Nontuberculous Mycobacterial Infection and Environmental Molybdenum in Persons with Cystic Fibrosis: A Case-Control Study in Colorado
NTM are ubiquitous environmental bacteria that may cause chronic lung disease and are one of the most difficult to treat infections among persons with cystic fibrosis (pwCF). We identified molybdenum in the source water as the most predictive factor of M. abscessus infection among pwCF in Colorado.
How this study originated
In the middle of my postdoctoral fellowship at National Jewish Health (NJH) in Denver, I was waiting for new funding so I could begin work on a project involving nontuberculous mycobacteria (NTM) disease. In the meantime, I thought it would be interesting to map out the locations of all the NTM cases seen at NJH, which is a national referral hospital. I wanted to identify environmental factors associated with NTM clustering because little is known about the environmental determinants of NTM. What was supposed to be a quick “in the meantime” project turned into years of exciting research.
Identifying NTM clusters
In our first paper, “A Geospatial Epidemiologic Analysis of Nontuberculous Mycobacterial Infection: An Ecological Study in Colorado,” we used spatial scan methods to identify statistically significant clusters of NTM cases. We found two significant clusters in Colorado. These clusters could not have been more geographically, climatically, and demographically different. The larger cluster (the western most cluster) was more rural, mountainous, at higher elevation, with wetter and cooler climates. The smaller cluster (the eastern most cluster) included more urban and suburban regions, at lower elevation, in drier and hotter climates. What stood out to me as the common factor connecting these clusters was the water supply: The smaller cluster encompassed urban regions and received the majority of its water from the mountainous and rural regions located within the larger cluster. Did something common to the water supply connect these two clusters? This realization and question set in motion our interest in examining water-quality constituents as environmental determinants of NTM infection.
Identifying water-quality constituents
A criticism of our prior work was the lack of a control group to use as a comparison for the NTM patients. The new study resolves that by including a unique dataset comprising all cystic fibrosis patients in Colorado. Any cystic fibrosis patient who had a positive NTM culture was included as a case in our study, whereas all cystic fibrosis patients with repeated negative cultures were included as controls. In a previous study (Lipner et al. Nontuberculous Mycobacterial Disease and Molybendum in Colorado Watersheds, Int J Environ Res Public Health. 2020 May 29;17(11):3854), we reported that molybdenum in surface water was significantly associated with increased risk of NTM infection. The new study contains species- specific case information categorized into two phenotypically distinct groups of NTM (Mycobacterium abscessus and Mycobacterium avium complex (MAC)). We identified that molybdenum in surface water was significantly associated with increased risk of Mycobacterium abscessus infection, but it did not increase the risk of MAC infection.
These studies are multidisciplinary. As a result, we relied heavily on the expertise of our collaborating scientists at the U.S. Geological Survey (Dr. Katherine Walton-Day and Dr. Carleton Bern). They helped identify water data entries that looked inaccurate and explained the geology and hydrology of Colorado. The nexus of these disciplines, linking hydrological and geological data to human infection of environmental infectious organisms, is an unexplored area of NTM research. Our conclusions provide hypotheses about the role of these trace metals in natural water sources and their possible affect on organism metabolism and pathogenesis. If these findings are confirmed experimentally, the concentrations of molybdenum in natural waters could potentially be used to identify regions that are high-risk for those susceptible to NTM infection. Those results could ultimately influence people’s decisions on where to reside. A pilot grant from the Cystic Fibrosis Foundation has enabled us to move this research forward and we’re finding that these results are not unique to Colorado. Stay tuned…!