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Nontuberculous Mycobacterial Pulmonary Disease

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Nontuberculous mycobacterial pulmonary disease is a broad term for a group of pulmonary disorders caused and characterized by exposure to environmental mycobacteria other than those belonging to the Mycobacterium tuberculosis complex and Mycobacterium leprae. Mycobacteria are aerobic, nonmotile organisms that appear positive with acid-fast alcohol stains. Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and have been recovered from domestic and natural water sources, soil, and food products, and from around livestock, cattle, and wildlife.1-3 To date, no evidence exists of human-to-human or animal-to-human transmission of NTM in the general population. Infections in humans are usually acquired from environmental exposures, although the specific source of infection cannot always be identified. Similarly, the mode of infection with NTM has not been established with certainty, but it is highly likely that the organism is implanted, ingested, aspirated, or inhaled. Aerosolization of droplets associated with use of bathroom showerheads and municipal water sources and soil contamination are some of the factors associated with the transmission of infection. Proven routes of transmission include showerheads and potting soil dust.2,3

NTM pulmonary disease occurs in individuals with or without comorbid conditions such as bronchiectasis, chronic obstructive pulmonary disease, pulmonary fibrosis, or structural lung diseases. Slender, middle-aged or elderly white females with marfanoid body habitus, with or without apparent immune or genetic disorders, showing impaired airway and mucus clearance present with this infection as a form of underlying bronchiectasis (Lady Windermere syndrome). It is unclear why NTM infections and escalation to clinical disease occur in certain individuals. Many risk factors, including inherited and acquired defects of host immune response (eg, cystic fibrosis trait and α1 antitrypsin deficiency), have been associated with increased susceptibility to NTM infections.4

NTM infection can lead to chronic symptoms, frequent exacerbations, progressive functional and structural lung destruction, and impaired quality of life, and is associated with an increased risk of hospitalization and higher 5-year all-cause mortality. As such, NTM disease is drawing increasing attention at the clinical, academic, and research levels.5 This case-based review outlines the clinical features of NTM infection, with a focus on the challenges in diagnosis, treatment, and management of NTM pulmonary disease. The cases use Mycobacterium avium complex (MAC), a slow-growing mycobacteria (SGM), and Mycobacterium abscessus, a rapidly growing mycobacteria (RGM), as prototypes in a non–cystic fibrosis, non-HIV clinical setting.

Epidemiology

Of the almost 200 isolated species of NTM, the most prevalent pathogens for respiratory disease in the United States are MAC, Mycobacterium kansasii, and M. abscessus. MAC accounts for more than 80% of cases of NTM respiratory disease in the United States.6 The prevalence of NTM disease is increasing at a rate of about 8% each year, with 75,000 to 105,000 patients diagnosed with NTM lung disease in the United States annually. NTM infections in the United States are increasing among patients aged 65 years and older, a population that is expected to nearly double by 2030.7,8

Isolation and prevalence of many NTM species are higher in certain geographic areas of the United States, especially in the southeast. The US coastal regions have a higher prevalence of NTM pulmonary disease, and account for 70% of NTM cases in the United States each year. Half of patients diagnosed with NTM lung disease reside in 7 states: Florida, New York, Texas, California, Pennsylvania, New Jersey, and Ohio, with 1 in 7 residing in Florida. Three parishes in Louisiana are among the top 10 counties with the highest prevalence in United States. The prevalence of NTM infection–associated hospitalizations is increasing worldwide as well. Co-infection with tuberculosis and multiple NTMs in individual patients has been observed clinically and documented in patients with and without HIV.9,10

It is not clear why the prevalence of NTM pulmonary disease is increasing, but there may be several contributing factors: (1) an increased awareness and identification of NTM infection sources in the environment; (2) an expanding cohort of immunocompromised individuals with exogenous or endogenous immune deficiencies; (3) availability of improved diagnostic techniques, such as use of high-performance liquid chromatography (HPLC), DNA probes, and gene sequencing; and (4) an increased awareness of the morbidity and mortality associated with NTM pulmonary disease. However, it is important to recognize that to best understand the clinical relevance of epidemiologic studies based on laboratory diagnosis and identification, the findings must be evaluated by correlating them with the microbiological and other clinical criteria established by the American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) guidelines.11

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