Pathogenesis and Risk Factors for Nontuberculous Mycobacterial Lung Disease

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Key points

  • Nontuberculous mycobacteria (NTM) are ubiquitous in the environment, and yet NTM lung disease is relatively uncommon and is dominated by relatively few species of NTM.

  • These observations suggest that both host vulnerability and pathogen virulence factors are important determinants of whether infections become established.

  • There are risk factors for isolated NTM lung disease and disseminated disease as well as components of NTM cell envelope that are likely to play important pathogenic roles.

Known risk factors for nontuberculous mycobacteria lung disease

NTM lung disease occurs primarily in 3 broad groups of patients (Fig. 1): (1) those with anatomic lung abnormalities that usually do not have an identifiable genetic basis (eg, localized bronchiectasis from prior unrelated infections, emphysema, and pneumoconiosis, such as silicosis),1, 2, 3 (2) those with immunologic or known or suspected genetic disorders that predispose to bronchiectasis and/or lung infections (eg, cystic fibrosis, primary ciliary dyskinesia, alpha-1-antitrypsin deficiency,

Nontuberculous mycobacteria lung disease in patients without a known underlying cause

The occurrence of NTM lung disease in individuals without any known predisposing condition is well known; it has been observed that not an insignificant number of these patients possess a lifelong slender body habitus and thoracic cage abnormalities, such as pectus excavatum and scoliosis.10, 12, 13, 14, 15

A plausible mechanism by which slender individuals with low body fat content may be predisposed to NTM infections is relative deficiency of leptin, an adipokine whose canonical function is

Known risk factors for visceral or disseminated nontuberculous mycobacteria disease

Patients with visceral or disseminated NTM disease are almost always frankly immunocompromised, such as those receiving tumor necrosis factor-alpha (TNFα) antagonists, organ transplant recipients, and patients with untreated AIDS (Table 2). Although rare, certain inherited disorders can also predispose to NTM and are termed mendelian susceptibility to mycobacterial diseases (MSMD) (see Table 2). These experiments-of-nature provide great insights into which elements of the immune system are host

Pathogenesis of centrilobular nodules, bronchiectasis, and cavities in nontuberculous mycobacteria lung disease

The hallmark radiographic features of NTM lung disease include bronchiectasis, nodules, tree-in-bud opacities (branching centrilobular nodules) with and without cavities, atelectasis, ground-glass opacities, and/or consolidation. Correlation of these radiographic features with histopathology can help elucidate the cellular pathogenesis of NTM lung disease, independent of any underlying predisposing condition.26, 27, 28 In resected lung tissues, computed tomography findings of bronchiectasis and

Pathogenesis of nontuberculous mycobacteria infection of host cells

Given the airway-centric nature of NTM infection in the lungs, it is not surprising that NTM can infect bronchial epithelial cells. Fibronectin-attachment protein is present on the surface of M avium and, by binding to fibronectin on mucosal surfaces, serves to facilitate more specific mycobacterial binding to integrin receptors.31 Bacilli that have gained entry into epithelial cells undergo a phenotypic change that results in greater efficiency at invading macrophages.31 Biofilm formation and

Lipids of Nontuberculous Mycobacteria

NTM-specific virulence factors likely help drive the establishment and progression of disease (Fig. 3). This notion is supported by the fact that, even though more than 160 species of NTM are identified, most diseases are caused by relatively few species. The most widely recognized virulence factor of the Mycobacterium genus is its waxy cell envelope that protects against antibiotics and host immune defenses as well as facilitates survival in soil and water. Lipids of various composition

Summary

In summary, multiple factors are necessary for the pathogenesis of NTM lung disease, including sufficient environmental exposure, host susceptibility factors, and mycobacterial virulence factors. In patients without an obvious host risk factor, the observation that a significant number possess a unique body morphotype and immunophenotype suggests an unidentified host risk factor. The contribution of NTM-derived cell envelope lipids to the pathogenesis of NTM lung disease needs further

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  • Cited by (107)

    • Sex, ancestry, senescence, and aging (SAnSA) are stark drivers of nontuberculous mycobacterial pulmonary disease

      2022, Journal of Clinical Tuberculosis and Other Mycobacterial Diseases
      Citation Excerpt :

      Susceptibility also extends to individuals with prior lung infections, bronchiectasis, and genetic diseases such as cystic fibrosis, alpha-1 antitrypsin deficiency, and primary ciliary dyskinesia [8]. These vulnerabilities and other exposures have been previously reviewed in the literature [9–10]. In the United States (U.S.), the incidence of NTM infections has increased from 1.6 to 1.8 cases per 100,000 persons in the 1980′s [11], to 8.7 cases per 100,000 persons in 2008, and to 13.9 cases per 100,000 persons in 2013 [12].

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    Disclosures: none.

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