Familial clustering of pulmonary nontuberculous mycobacterial disease

Abstract

Background: Nontuberculous mycobacteria (NTM) are environmental organisms associated with pulmonary disease without person-to-person transmission. Although genetic causes of disseminated NTM infection are well characterized, genetic causes for most human susceptibility to pulmonary NTM infection have not been determined.

Methods: Family histories for relevant disease characteristics were obtained as part of an ongoing natural history study. Six families were identified in which at least two blood relatives had pulmonary NTM. A systematic review of medical records extracted data relevant to pulmonary infection and baseline demographics. Data were reconfirmed by telephone interviews.

Results: Familial clustering of pulmonary NTM was proven in six families. Four of the families were white, and the majority of affected individuals were women. The average age at diagnosis was 56.4 +/- 10.7 years, the average height was 167.5 +/- 8.7 cm, and the mean BMI was 22.0 +/- 2.98 kg/m(2). Scoliosis was present in 31%. Five of 12 patients had cystic fibrosis transmembrane conductance regulator gene variations, but none had classic cystic fibrosis. Infections were caused by both slow and rapid growing mycobacteria, including Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium kansasii, Mycobacterium abscessus, and Mycobacterium massiliense. Family members were typically infected with different species of NTM.

Conclusion: We identified six familial clusters of pulmonary NTM infection, suggesting that there are genetic factors contributing to host susceptibility to pulmonary infection with NTM among some individuals with nodular bronchiectatic disease.

Figure 1.

Pedigrees of familial clusters of pulmonary NTM disease. MTB = Mycobacterium tuberculosis; NTM = nontuberculous mycobacteria.

Figure 2.

Representative CT scans of the chest demonstrating characteristic radiographic manifestations of pulmonary nontuberculous mycobacteria disease, including: multilobar nodules and bronchiectasis (arrowheads), patient 1.II.2 (A) and patient 2.I.2 (B); extensive bronchiectasis and cavity formation (arrow), architecture distortion, calcified hilar nodes, pleural thickening with marked left volume loss, patient 4.I.1 (C); diffuse bronchiectasis, bronchiolectasis, and scattered nodules, patient 3.I.2 (D).