Faculty Bibliography

BACKGROUND/UNASSIGNED:Nontuberculous mycobacteria pulmonary disease (NTM PD) has been increasing in the United States, and New York City is an important hotspot, with a high burden of disease. RESEARCH QUESTION/UNASSIGNED:We assessed how neighborhood-level risk factors influenced NTM PD prevalence in New York City. STUDY DESIGN AND METHODS/UNASSIGNED:We used outpatient claims data from hospitals participating in the Patient-Centered Outcomes Research Institute network, compiled by the INSIGHT Clinical Research Network at Weill Cornell Medicine. NTM PD period prevalence (referred to here as 'prevalence') was estimated by New York City neighborhood for the study period 2012 through 2022. A case was defined as someone with at least one claim for NTM PD. De-identified NTM PD case data and demographic data were analyzed by neighborhood of residence at diagnosis. Using prevalence estimates, we detected high- and low-prevalence regions within New York City and associated these estimates with demographic, clinical, socioeconomic, and environmental neighborhood-level factors using Poisson regression and backward elimination of covariates. RESULTS/UNASSIGNED:Overall, 6,169 NTM PD cases were identified among persons receiving care across 17 private New York City hospitals. The mean age was 67.5 years, 68.7% were female, and 57.3% were White. Over the study period, NTM PD prevalence increased throughout New York City, and median year built of housing units, median income, and median age of residents were significant neighborhood-level risk factors. The highest prevalence neighborhoods were in Manhattan, while the lowest prevalence neighborhoods were in Brooklyn and Staten Island. INTERPRETATION/UNASSIGNED:Our findings indicate that neighborhood-level access to care may explain the heterogeneity in NTM PD prevalence among New York City neighborhoods, as higher income, newer neighborhoods exhibited the highest NTM PD prevalences. Future studies should examine the extent of undetected NTM PD in New York City, particularly in low-income areas.

RATIONALE/BACKGROUND:The discoveries of neutrophilic inflammation and Pseudomonas-dominant pulmonary dysbiosis have helped pave the way for host-directed therapy in bronchiectasis. Substantial knowledge gaps still remain about the interplay between neutrophilic signatures and microbes in non-tuberculous mycobacterial lung disease (NTM-LD), a phenotypically diverse lung infection that is increasingly prevalent in the United States and other parts of the world. OBJECTIVES/OBJECTIVE:Evaluate the lower airway microbiota and neutrophilic traits in NTM- and NTM+ bronchiectasis. METHODS:16S rRNA gene sequencing, cell counts, and neutrophil extracellular trap (NET) immunoassays were performed on bronchoscopic lower airway samples in 200 bronchiectasis subjects (108 NTM-, 92 NTM+). A preclinical model of oral commensal micro-aspiration and NTM infection was used to profile the murine lower airways with flow cytometry and a NET assay. MEASUREMENTS AND MAIN RESULTS/RESULTS:Lower airways of NTM+ bronchiectasis patients were enriched with Mycobacterium and oral commensals (e.g., Veillonella, Prevotella and Streptococcus). NET levels were higher in NTM+ BAL. Mycobacterium and oral commensals co-occurred with NET and neutrophils in network studies. Distinct oral commensal taxa were associated with severe disease phenotypes such as cavitary disease and exacerbators. In a murine micro-aspiration model, the combination of oral commensals and Mycobacterium led to a sustained pro-inflammatory immune response marked by an increase in Th17, γδT cells, PD-1+ T lymphocytes as well as higher NET levels. CONCLUSIONS:Our analyses showed that distinct microbiome features beyond the primary pathogen can contribute to neutrophilic inflammation and severe disease phenotypes in bronchiectasis/ NTM-LD.