Chest
Volume 137, Issue 3, March 2010, Pages 629-634
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Original Research
Lung Infection
Familial Clustering of Pulmonary Nontuberculous Mycobacterial Disease

https://doi.org/10.1378/chest.09-1173Get rights and content

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/m2. 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.

Section snippets

Materials and Methods

As part of an Institutional Review Board-approved natural history study of mycobacterial disease at the NIH family histories for relevant disease characteristics were obtained. From a cohort of approximately 120 patients who met the American Thoracic Society disease criteria without known cystic fibrosis or primary ciliary dyskinesia, six families had at least two members affected with pulmonary NTM.8 A systematic review of the medical records was performed and patients were interviewed to

Results

Sibling pairs were the most commonly affected family members (see Fig 1). However, two mother-child pairs were also identified, and an additional mother (1.I.2) was reported to have had pulmonary NTM disease. Four of the six families were white, and 10 of 13 patients (77%) were women (Table 1). All patients seen at NIH lived in coastal US states, but none of the relative pairs resided in the same household at the time of diagnosis and several lived in different states. The average age of

Discussion

We identified six unrelated families in which pulmonary NTM disease affects at least two first-degree relatives. The patterns of transmission are consistent with dominant (parent-child) and recessive (siblings only) modes of inheritance. The fact that in several families cases were infected with distinct species of NTM suggests that neither common source exposure nor patient-to-patient intrafamily transmission was responsible. Therefore, these patients support the hypothesis that some pulmonary

Acknowledgments

Author contributions: Dr Olivier had full access to the data in this study and takes responsibility for the integrity of the data and accuracy of the analysis.

Dr Colombo: contributed to conducting the record review, contacting the participants to verify and obtain additional information, analyzing the data, creating the table and figures, and drafting the manuscript.

Dr Hill: contributed to reviewing and scoring all the scoliosis films, reviewing and interpreting selected chest CT scans for each

References (0)

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

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    Genome wide-association studies (GWAS) have identified genetic variants associated with susceptibility to idiopathic pulmonary fibrosis (IPF) in people of European ancestry [25]. While the literature regarding the role of ancestry in NTM PD remains scant, NTM PD has been reported among families including a pair of siblings in Japan as well Korean, Caucasian, and Hispanic families in the U.S., suggesting there may be a heritable, genetic contribution to NTM PD [26–27]. While resident Asians in geographic hot spots for NTM like Hawai’i show the highest period prevalence of NTM PD, disease is lowest among Native Hawaiian and other Pacific Islanders [28].

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Funding/Support: This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestpubs.org/site/misc/reprints.xhtml).

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