Faculty Bibliography

INTRODUCTION/BACKGROUND:with dysglycemia, it remains unknown if reducing air pollution exposure through air filtration can affect improvements in glucose. This study aims to test the hypothesis that short-term, in-home air pollution reduction using high efficiency particulate air (HEPA) filtration will improve blood sugar in adults with prediabetes. METHODS AND ANALYSIS/METHODS:as the independent variable. ETHICS AND DISSEMINATION/BACKGROUND:This study has undergone peer review; and the work was supported by Grant 2023-0214 from the Doris Duke Foundation, who had no other role in study design or implementation. The study was registered in ClinicalTrials.gov (NCT05994937) prior to recruitment.

Occupational exposure to commercial cooking emissions has not been comprehensively studied, particularly in a Western context. This investigation measured the concentration and composition of volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), particulate matter (PM), carbon monoxide (CO), and black carbon (BC) in 18 New York City restaurants. Eight-hour gravimetric PM_1,2.5,10 mass concentrations were measured in kitchen and dining areas, and PM₁ was speciated using X-ray fluorescence. Evacuated canisters and XAD-2 sorbent tubes collected VOCs and PAHs, respectively, and were speciated using gas chromatography/mass spectrometry (GC/MS). Lastly, spatial concentration gradients for PM_2.5 and day-of-the-week effects were considered in eight additional restaurants. A median PM_2.5 concentration of 79.6 μg/m³ was found in kitchens, with real-time values spiking into the thousands of micrograms per cubic meter in some restaurants─values below the Occupational Safety and Health Administration 8 h permissible exposure limit of 5 mg/m³ for particles not otherwise regulated (respirable fraction), but well above the 24 h World Health Organization recommended ambient exposure limit of 15 μg/m³ for 2021. Benzene, a known carcinogen, was frequently detected in the kitchen areas, while PAHs were often undetected. These data warrant further investigation into the cardiopulmonary health of restaurant workers.

OBJECTIVE/UNASSIGNED:The aim of this laboratory study was to characterize the effects of sub-chronic electronic cigarette (E-cig) aerosol exposures on genome-wide DNA methylation in mice to begin to elucidate the pathophysiology of E-cig-related pulmonary diseases and cancer. MATERIALS AND METHODS/UNASSIGNED:Male C57BL/6 and FVBN mice were randomly assigned to one of two treatment groups (n = 6 per group) and exposed daily to either filtered air or a 50:50 mixture of propylene glycol and vegetable glycerol containing 24 mg/mL nicotine (+Nic). Whole-body inhalation exposures were conducted for 3 h/d, 5 d/week, for a total of 1-month. Sequences for ∼285 000 CpG probes were aligned to the mouse genome, and mixed linear models were used to model DNA methylation levels (β values). These evaluations were followed by ingenuity pathway analysis (IPA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) analysis. RESULTS AND DISCUSSION/UNASSIGNED:E-cig inhalation exposure induced significant DNA methylation changes in adult male mice, with a notable impact on cancer-related pathways. A total of 2300 genes in C57BL/6 mice and 6732 genes in FVBN mice were hypomethylated, while 1673 and 5529 genes were hypermethylated, respectively. KEGG and GO analyses highlighted key pathways such as Wnt/β-catenin signaling and proteoglycans in cancer, suggesting that E-cig aerosol exposure could disrupt critical genomic regulation and potentially promote carcinogenesis. These in vivo findings underscore the potential cancer-promoting effects of E-cig aerosols through epigenetic modifications. CONCLUSIONS/UNASSIGNED:Findings from this study provide compelling evidence that sub-chronic E-cig exposure induces genomic DNA methylation changes linked to cancer pathways in two strains of adult male mice, highlighting the serious adverse consequences of E-cig use and strain-specific response differences.

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.

INTRODUCTION/BACKGROUND:Elevated concentrations of air pollutants in residential neighborhoods are associated with poorer survival, cognitive, and cardiovascular health among older adults. Older kidney transplant (KT) recipients may be more vulnerable due to chronic immunosuppression and age-related co-morbidities. Therefore, we quantified the associations between pollutant concentrations and post-KT outcomes among older recipients. METHODS:]) were obtained from the Center for Air, Climate and Energy Solutions, and matched by ZIP code and year of KT. We used shared frailty models (cluster = state) to estimate the adjusted hazard ratios (aHR) of mortality and death-censored graft failure (DCGF) and competing risk models with cluster-robust standard errors to estimate the adjusted subhazard ratios (aSHR) of dementia and stroke by pollutant concentrations. RESULTS:concentrations were associated with a 3% (aSHR = 1.03, 95% CI: 1.00-1.07) and 4% higher risk of stroke (aSHR = 1.04, 95% CI: 1.02-1.07), respectively. CONCLUSION/CONCLUSIONS:Residence in neighborhoods with high concentrations of ambient air pollutants can worsen patient and graft survival, as well as increase the risk of stroke among older KT recipients. Early screening and interventions targeting older recipients living in such neighborhoods may be crucial for preserving cognitive and cerebrovascular health, as well as improving longitudinal quality of life.

RATIONALE & OBJECTIVE/UNASSIGNED:exposure and mortality, overall and by race and ethnicity. STUDY DESIGN/UNASSIGNED:Cohort study (2003-2019). SETTING & PARTICIPANTS/UNASSIGNED:National registry for patients with kidney failure. EXPOSURES/UNASSIGNED:), segregation scores (Theil's H method), deprivation scores (American Community Survey), and built environment factors (medically underserved areas [MUA] and urbanicity) by patients' residential ZIP code at dialysis initiation. OUTCOME/UNASSIGNED:All-cause mortality. ANALYTICAL APPROACH/UNASSIGNED:and mortality, overall and stratified by race and ethnicity. RESULTS/UNASSIGNED:< 0.001]). LIMITATIONS/UNASSIGNED:may not reflect individual-level exposures. CONCLUSIONS/UNASSIGNED:and reduce related mortality.

BACKGROUND:on dementia may be more severe in this population. METHODS:and dementia risk factors using a Wald test. Models were adjusted for confounders, including social determinants of health. RESULTS:was associated with 1.90-fold higher odds of global cognitive impairment (95% CI: 1.48-2.46), and 3.29-fold higher risk of dementia (95% CI: 1.14-9.55). CONCLUSION/CONCLUSIONS:neighborhoods should discuss cognitive assessments and ways to increase physical activity with providers.

BACKGROUND/UNASSIGNED:; environmental injustice) by racial/ethnic segregation (social injustice) on dementia diagnosis in ESKD. METHODS/UNASSIGNED:concentrations (annualized and matched to older adults' residential ZIP code at dialysis initiation) and by segregation scores (Theil's H method). FINDINGS/UNASSIGNED:and segregation. INTERPRETATION/UNASSIGNED:experienced an increased risk of dementia; this risk was particularly pronounced among individuals in high segregation and predominantly minority neighborhoods. Environmental and social injustices likely drive racial and ethnic disparities in dementia for older adults with ESKD, underscoring the need for interventions and policies to mitigate these injustices. FUNDING/UNASSIGNED:National Institutes of Health.