Hepatic arterial infusion (HAI) is an established treatment for patients with unresectable colorectal liver metastases (uCRLM). Until recently, HAI was only performed at a limited number of centers. We previously reported early outcomes suggesting that implementation of a new HAI program is safe and feasible. Here, we report perioperative and oncologic outcomes from an expanded series of patients with uCRLM treated with HAI. We analyzed outcomes from consecutive patients with uCRLM who underwent HAI pump (HAIP) placement at Duke University Hospital from 2018 to 2023. Demographics, prior treatment, and perioperative and oncologic outcomes were assessed. Overall, 102 patients underwent HAIP placement for uCRLM; 62

Rationale: The identification of early chronic obstructive pulmonary disease (COPD) is essential to appropriately counsel patients regarding smoking cessation, provide symptomatic treatment, and eventually develop disease-modifying treatments. Disease severity in COPD is defined using race-specific spirometry equations. These may disadvantage non-White individuals in diagnosis and care. Objectives: Determine the impact of race-specific equations on African American (AA) versus non-Hispanic White individuals. Methods: Cross-sectional analyses of the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) cohort were conducted, comparing non-Hispanic White (n = 6,766) and AA (n = 3,366) participants for COPD manifestations. Measurements and Main Results: Spirometric classifications using race-specific, multiethnic, and "race-reversed" prediction equations (NHANES [National Health and Nutrition Examination Survey] and Global Lung Function Initiative "Other" and "Global") were compared, as were respiratory symptoms, 6-minute-walk distance, computed tomography imaging, respiratory exacerbations, and St. George's Respiratory Questionnaire. Application of different prediction equations to the cohort resulted in different classifications by stage, with NHANES and Global Lung Function Initiative race-specific equations being minimally different, but race-reversed equations moving AA participants to more severe stages and especially between the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0 and preserved ratio impaired spirometry groups. Classification using the established NHANES race-specific equations demonstrated that for each of GOLD stages 1-4, AA participants were younger, had fewer pack-years and more current smoking, but had more exacerbations, shorter 6-minute-walk distance, greater dyspnea, and worse BODE (body mass index, airway obstruction, dyspnea, and exercise capacity) scores and St. George's Respiratory Questionnaire scores. Differences were greatest in GOLD stages 1 and 2. Race-reversed equations reclassified 774 AA participants (43%) from GOLD stage 0 to preserved ratio impaired spirometry. Conclusions: Race-specific equations underestimated disease severity among AA participants. These effects were particularly evident in early disease and may result in late detection of COPD.

Introduction: Chimeric Antigen Receptor (CAR)- T cell therapy has revolutionized the treatment of hematologic malignancies. However, access to CAR-T therapy remains limited, especially for underserved populations. We hypothesize that disparities in age, gender, race, and insurance type affect access and progression through key stages of CAR-T therapy-referral, evaluation, and infusion of CAR- T cells. These disparities contribute to inequities in the utilization of CAR-T therapy. Method: This retrospective study analyzed data from July 2019 to June 2022, incorporating records from the North Carolina Central Cancer Registry (NCCCR) and Duke Cancer Institute. The study focused on adults aged 19-79 with lymphoma or multiple myeloma residing in 67 North Carolina counties, which are designated as Duke's primary catchment area. Cohort 1 comprised NCCCR-Eligible patients-those identified in the NCCCR dataset as eligible for CAR-T infusion. Cohort 2 included Duke Referred patients, further divided into: 2A) Referral Only-patients who were referred but did not receive an appointment; 2B)Appointment without infusion-patients who had an appointment but did not receive CAR-T therapy; and 2C) CAR-T -patients who underwent CAR-T infusion. Statistical analyses included chi-square tests, ANOVA or Wilcoxon Signed Rank tests, and logistic regression. Referrals to other centers within the DCI catchment and out-of-state counties were excluded from the study. Results: NCCCR eligible vs. Duke Referred (Cohort 1 vs 2): Comparing the NCCCR cohort with CAR-T candidates referred to Duke, Duke referrals are younger median 64 [22-79] versus 66 years [19-79] in NCCCR, p = 0.004) and with fewer Caucasian/White patients (60% DCI vs. 71% NCCCR) and more Black or African American (30% DCI vs. 24% NCCCR). Private insurance is higher at DCI (50% vs. 31% NCCCR). Both cohorts are predominantly in metropolitan areas (81% DCI vs. 78% NCCCR, p < 0.001) and Medicare was less common than in NCCCR (40%, vs. 53%, p<0.001). DCI has a higher median income ($67,000 vs. $58,646, p < 0.001) and a lower social vulnerability index (0.61 vs. 0.66, p < 0.001). Referral Only vs Appointment without Infusion (Cohort 2A vs. 2B): Analysis of the referral-only cohort versus those who attended an initial evaluation appointment for CAR-T revealed significant sociodemographic differences. African Americans were more prevalent among the referral-only group (37% vs. 30%, p = 0.004) and had lower odds of attending initial evaluation appointments (OR = 0.55, 95% CI [0.35-0.87], p = 0.010). Univariate analysis indicated that a lower proportion of the referral-only group had private insurance (44% vs. 49%, p = 0.007) and Medicare coverage (40% vs. 44%, p = 0.007). However, these differences did not persist in multivariate analysis (OR = 0.78, 95% CI [0.49-1.23], p = 0.3 for Medicare). Non-private, non-Medicare insurance showed a trend towards lower attendance at initial appointments (OR = 0.35, 95% CI [0.14-1.03], p = 0.040), but this trend was not significant, likely due to the small sample size. The median time to appointment was 20 days (range 1-253). Age, sex, RUCA classification, income, and social vulnerability index did not show significant effects (p > 0.1). Appointment without Infusion vs CAR-T (Cohort 2B vs. 2C): Comparison of patients evaluated without infusion versus CAR-T recipients revealed higher odds of proceeding to CAR-T for males (OR = 2.68, 95% CI [1.63-4.56], p < 0.001) and Black or African American patients (OR = 1.87, 95% CI [1.06-3.23], p = 0.027). The median time to CAR-T was 141 days (range 41-1,248). No significant differences were observed in age, insurance type, RUCA classification, income, or social vulnerability index. Conclusion: Barriers to CAR-T therapy access at Duke appear to vary by stage. Initially, African American race and non-private insurance are linked to lower attendance at evaluation appointments post-referral. After evaluation, female gender and African American race are associated with a lower likelihood of proceeding to CAR-T infusion, highlighting significant gender and racial disparities. Further research is needed to determine if these disparities are due to demographic, socioeconomic, or healthcare system factors. Tailored interventions and collaborations with community partners and patient navigators are crucial for addressing these disparities and ensuring equitable access to CAR-T therapy.

Abstract Disclosure: J.G. Kallet: None. W. Hover: None. A. Krein: None. M. Lowe: None. M.F. Slovick: None. G. Kinney: None. S. Majka: None. K. Warren: None. S. Watts: None. M.T. McDermott: None. E.A. Regan: None. Multiple studies have shown reduced quality of life in people with adrenal insufficiency based on 1- 4 week recall of symptoms. However, “within-day” symptoms are commonly reported to treating physicians, and there is no clear understanding of what these symptoms represent for quality of life or adequate disease management. Lack of adequate cortisol has been postulated as a factor for both persistent symptoms and reduced quality of life but dose adjustment is not typically prescribed. Within-day symptoms are similar to those reported prior to treatment, and include lack of energy, nausea, vomiting, anorexia, headache, dizziness, shakiness, muscle cramps, and cognitive impairments. Addressing the relationship between “within-day” symptoms and replacement dosing could improve disease management. Further, understanding the association of within-day symptoms to outcomes (quality of life and adrenal crises) provides an impetus to change the standard of care. Individuals enrolled in the MyAI registry provided information about “within-day” symptoms. These included energy to accomplish tasks, cognitive symptoms, and overall symptoms. The questions were scored with increased values representing greater and more frequent symptoms and were summed to create a severity score. Patients also reported adrenal crisis within the past year and completed the AddiQoL as quality of life over the past 4 weeks.Responses were obtained from 712 adult registry participants - 84% female, age range 23-89, mean 51.2 (15.2) years - and 47% reported an adrenal crisis within the past year. Within-day symptom score range was 3-15 points with mean 7.9 and SD of 2.96. Higher “within-day” symptom scores were associated with stepwise reductions in the AddiQoL (worse quality of life). Individuals who reported an adrenal crisis within the past year had significantly increased symptom scores [8.8 (2.9) vs 6.7 (2.5), p<0.0001]. Regression model for the AddiQoL total score (R2 = 0.8) found after adjusting for group, age and sex, that BMI (p = 0.0002) and symptom score (p<0.0001) were highly significant predictors of worse AddiQoL score. ConclusionAdrenal crisis is reported frequently by patients who are being treated for adrenal insufficiency. We found a strong association of “within-day” symptoms to both risk of adrenal crisis and reduced quality of life. Addressing persistent disease-related symptoms in adrenal insufficiency would be an appropriate disease management response to improve care. The initial choice of replacement dosing based on body surface area or other metric may be a starting point for care but should be informed by studies that show large variation in absorption and metabolism between individuals. Adjusting doses of replacement hormones and careful management of adrenal insufficiency symptoms could improve outcomes. Presentation: 6/1/2024

Background: Hematopoietic Stem Cell Transplantation (HCT) is a life-saving treatment for many patients with hematologic malignancies. Disparities persist across the transplant continuum. We hypothesize that sociodemographic factors disproportionately impact referral rates and completion of HCT. Understanding these disparities is essential for developing effective strategies to improve HCT access and mitigating healthcare inequities among patients with hematologic malignancies. This study assesses how social factors are associated with referral by primary hematologists, patient attendance at HCT evaluation, and receipt of HCT among North Carolina residents within our catchment area. Method: This retrospective study utilized data covering July 2019 to June 2022 from the North Carolina Central Cancer Registry (NCCCR) and Duke Cancer Institute (DCI) for adults aged 19-79 with HCT-eligible hematologic malignancies in 67 North Carolina counties designated as DCI's primary catchment area. Cohort 1includes NCCCR-Eligible patients (N = 8,557)-eligible for HCT in the NCCCR dataset. Cohort 2 includes Duke Referred patients (N = 761)-referred to Duke for HCT, further divided into: 2A) Referral Only (N = 124)-referred but did not receive an appointment; 2B)Appointment Only (N = 471)-had an appointment but did not undergo HCT; 2C) Transplanted (N = 166)-received HCT. Statistical analyses included chi-square, ANOVA, Wilcoxon Signed Rank tests, and logistic regression. Referrals to other centers within the DCI catchment and out-of-state counties were excluded. Result: NCCCR eligible vs. Duke Referred (Cohort 1 vs 2): Duke-referred patients were younger (median age 64 vs. 66 years, p = 0.004), had a higher percentage of African Americans (30% vs. 24%, p < 0.001), and had higher median income ($67,000 vs. $58,546, p < 0.001). They also had better access to resources (lower social vulnerability: 0.66 vs. 0.68, p < 0.001) and higher private insurance coverage (50% vs. 31%, p < 0.001). Additionally, a higher proportion of Duke-referred patients had Multiple Myeloma (48% vs. 28%, p < 0.001) and a lower proportion had Lymphoma (28% vs. 43%, p < 0.001) compared to the NCCCR cohort. Referral Only vs. Appointment Only (Cohort 2A vs 2B): Non-Caucasian/Non-African-American patients were less likely to attend their initial evaluation appointments (OR 0.35, 95% CI[0.19-0.66], p < 0.001), as were those with non-private or non-Medicare insurance (OR 0.45, 95% CI [0.22-0.96], p = 0.032). Although the Referral Only cohort had a higher proportion of African Americans (37% vs. 30%, p = 0.004) and showed a trend toward greater overall vulnerability (0.73 vs. 0.66, p = 0.045), these differences were not significant in multivariate analysis (African Americans: OR 0.66, 95% CI [0.42-1.06], p = 0.082; overall vulnerability: OR 0.02, 95%CI [0.00-1,484], p = 0.50). Other factors, including age, gender, income, and RUCA status, did not affect appointment attendance. Appointment-Only vs. Transplant Receipt (Cohort 2B vs 2C): Patients who only attended the initial appointment were older (median age 65 vs. 62 years, p = 0.002) and had a lower proportion under 65 (48% vs. 61%, p < 0.001). Multivariable analysis showed less likely receipt of transplant after appointment for patients >=70 years of age (vs. <=60, OR 0.34, 95% CI [0.18-0.62], p < 0.001). A higher proportion of those without a transplant had Medicare insurance (44% vs. 33%, p = 0.002), but this difference did not show clinical significance in multivariate analysis (OR 0.84, 95% CI [0.53-1.31], p = 0.40). However, those with non-private or Medicare insurance who attended the initial evaluation appointment had a higher likelihood of proceeding to HCT (OR 2.54, 95% CI [1.20-5.35], p = 0.014). Conclusion: Our analysis reveals barriers for non-Caucasian and non-African American patients and those with non-private or Medicare insurance, impacting access to initial HCT evaluations. While these factors hinder progression to evaluation, overcoming early barriers may improve access to HCT. To ensure equity, we must address insurance disparities, implement financial assistance programs, and tailor outreach for minoritized racial groups. These steps are crucial for achieving equitable access to HCT therapy for all patients.

MET amplification (amp) is a driver of acquired resistance to epidermal growth factor receptor (EGFR) antibodies in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC). Savolitinib is an oral small molecule tyrosine kinase inhibitor that has demonstrated anti-tumor activity in MET-driven advanced solid tumors. We report the results of a phase 2 study of savolitinib in patients with mCRC with MET amp detected by circulating cell free (cf)DNA. Patients with chemotherapy refractory mCRC and MET amp detected by cfDNA were treated with savolitinib until unacceptable toxicity or disease progression. The primary endpoint was objective response rate. Secondary endpoints were clinical activity and safety. Five patients were enrolled and treated. Best overall response was stable disease (SD) in two patients, progressive disease (PD) in two patients, and one patient unevaluable for response. The majority of treatment-emergent adverse events (TEAEs) were grade 1 or 2. The most common TEAEs included fatigue (n = 3) and nausea (n = 3). There were no grade 4 or 5 TEAEs. Savolitinib was well tolerated; however, in this small group of biomarker-selected patients, we observed no evidence of anti-tumor activity. Clinicaltrials.gov Identifier: NCT03592641. Registered on July 17, 2018.

BACKGROUND:Despite institutional perioperative bundles and national infection prevention guidelines, surgical site infection (SSI) after a major abdominal operation remains a significant source of morbidity. Negative pressure therapy (NPT) has revolutionized care for open wounds but the role of closed incision NPT (ciNPT) remains unclear. STUDY DESIGN:We conducted a multi-institutional randomized controlled trial evaluating SSI after major elective colorectal or hepatopancreatobiliary surgery (Clinical Trial Registration: NCT01905397). Patients were randomized to receive conventional wound care vs ciNPT (Prevena Incision Management System, 3M Health Care, San Antonio, TX). The primary endpoint was postoperative incisional SSI. SSI incidence was evaluated at inpatient days 4 or 5 and again at postoperative day 30. With 144 patients studied, the estimated power was 85% for detecting a difference in SSIs between 17% and 5% (conventional vs ciNPT; 1-sided α = 0.1). Secondary endpoints included SSI type, length of stay, 30-day readmission, and mortality. T-tests were used to compare continuous variables between treatments; similarly, chi-square tests were used to compare categorical variables. A p value of <0.05 was considered significant, except in the primary comparison of incisional and organ SSIs. RESULTS:During the 2013 to 2021 time period, 164 patients were randomized, and of those, 138 were evaluable (ciNPT n = 63; conventional n = 75). Incisional SSIs occurred in 9 (14%) patients in the ciNPT group and 13 (17%) patients in the conventional group (p = 0.31). Organ or space SSIs occurred in 7 (11%) patients in the ciNPT group and 10 (13%) in the conventional therapy group (p = 0.35). CONCLUSIONS:In this multi-institutional, randomized controlled trial of patients undergoing colorectal or hepatopancreatobiliary surgery, incidence of incisional SSIs between ciNPT and conventional wound therapy was not statistically significant. Future trials should focus on patient populations undergoing specific procedures types that have the highest risk for SSI.

e21510 Background: Patients (Pts) with metastatic melanoma presenting with brain metastases (MBM) have a high morbidity and mortality risk. The combination of ipilimumab/nivolumab (I/N) has demonstrated high intracranial response rates in selected, asymptomatic pts, suggesting there is a subset of pts who may be able to forgo or delay intracranial therapies. There is currently limited real world data on how many pts with MBM are successfully treated with this approach. We sought to explore our clinical experience at Duke University with combination immune checkpoint inhibitors for pts with MBM. Methods: An electronic database search was conducted for all metastatic melanoma pts treated with PD-1 therapies between 2015 and 2021. Pts treated with combination ICIs for brain metastases were included. The primary outcome was overall survival (OS). Secondary outcomes were need for local therapies (radiation (RT): stereotactic radiosurgery or whole brain radiation therapy or craniotomy), and immune related adverse events (irAEs). Results: Between 2015 and 2021, 66 pts with MBM received I/N, with a median follow-up of 30.4 months. Median age was 68, 60.6% were male and 61% had a BRAF mutation. 38 pts were asymptomatic. Of the 28 symptomatic patients 61% were on corticosteroids at the time of I/N initiation. 56% of pts received local therapy prior to start of I/N, 17% during and 18% after discontinuing I/N. 53% of pts were initiated on I/N as first line systemic therapy for MBM. 56% of patients had to discontinue I/N after one cycle because of high-grade irAEs. 13.8% of patients that received RT to the brain developed radionecrosis. Median OS was 25.6 months in the overall cohort, with a 1 year OS of 63%. There was a trend towards a higher risk of death for symptomatic versus asymptomatic patients HR:1.96 [95% CI: 0.96, 3.97; P:0.06]. Of the 38 asymptomatic patients, only 6 patients did not receive local therapies with either RT or craniotomy. Two of these patients died from melanoma progression, one from intra-cranial progression, the other from both intra-cranial and extra-cranial progression, and 4 remain alive without evidence of progression. Conclusions: The majority of pts with MBM are ultimately treated with multimodality therapy. Advances in systemic therapies have provided meaningful clinical benefit that could allow a limited number of asymptomatic patients to forgo local therapy, but currently few pts are treated in this manner.

Abstract Disclosure: W.J. Hover: None. K.E. Lowe: None. M.E. Lowe: None. J.G. Kallet: None. M.F. Slovick: None. S.L. Majka: None. M.T. McDermott: None. E.A. Regan: None. Individuals with adrenal insufficiency (AI) have been shown to have reduced quality of life in spite of hormone replacement. Although late-stage insufficiency and adrenal crisis may show signs including hypotension and electrolyte abnormalities, patient-reported symptoms may predict outcomes in AI and can be a key factor in understanding poor quality of life in adrenal insufficiency. The SF-36, a generic quality of life (QoL) survey has been reported in adrenal insufficiency but may lack disease-specific domains to define QoL deficits in AI. An AI disease-specific QoL survey, the AddiQoL has also been validated. We evaluated the AddiQol and SF-36 for distinguishing the health status of AI patients in terms of diagnosis, medication use and risk of crisis using a patient registry. Methods: We identified 344 individuals from the MyAI patient registry who had provided responses to both the AddiQoL and SF-36. We compared the AddiQoL overall score with three domains of the SF-36: physical function, role physical, vitality, and the physical and mental component scores (PCS and MCS). Results: Respondents were from all 50 US states with 83% female and mean (SD) age of 50 (15) years. AI diagnosis was Primary 63%, Central 32% and congenital adrenal hyperplasia 5% based on self-report and confirmation with medical records. Both the SF-36 and AddiQoL identified reduced QoL in the AI participants and were significantly correlated: PCS to AddiQoL 0.73 and MCS to AddiQoL 0.63. Role Physical, Vitality and General Health were the most reduced domains with mean values of 38.4 (43.5), 35.6 (24.5) and 40.8 (24.7) respectively. Primary AI showed significantly better QoL than Central AI by both SF-36 and AddiQol [80.3(15.1) vs 69.9 (14.2), p<0.001]. Respondents who reported an adrenal crisis within the past year had significantly lower AddiQol [72.8(15.4) vs 82.3 (15.4), p<0.001] and SF-36 scores. Respondents who were currently treated with hydrocortisone (HC) had better QoL than those on Prednisone [HC 78.1 (15.2), Prednisone 74.1 (15.9), p=0.02 adjusted for diagnosis group]. Conclusions: In a geographically broad cohort of US AI patients, we confirm significant reductions in QoL in spite of treatment. Both the SF-36 and AddiQoL were able to distinguish differences in QoL by diagnosis, risk of adrenal crisis and medication. Further work to define specific patterns of high-risk symptoms may improve early diagnosis of impending crisis. Presentation: Saturday, June 17, 2023

Background: Evaluation for activating mutations in KRAS, NRAS, and BRAF in colorectal cancer (CRC) and in KRAS in pancreatic ductal adenocarcinoma (PDAC) is essential for clinical care. Plasma cell-free DNA (cfDNA) next-generation sequencing (NGS) allows convenient assessment of a tumor's molecular profile, however low tumor DNA shedding limits sensitivity. We investigated mutant allele frequency (MAF) of other oncogenic dominant genes to identify a threshold for accurate detection of KRAS, NRAS, and BRAF (RAS/RAF) mutations in cfDNA. Methods: Molecular and clinical data were obtained from the Duke Molecular Registry of Tumors and the SCRUM-Japan GOZILA study. Patients with CRC or PDAC and a KRAS, NRAS, or BRAF activating single nucleotide variant (SNV) present on tissue NGS and with available cfDNA assays were included. Recursive partitioning and Wilcoxon-rank statistics methods identified potential cut-points for discriminative MAF values. Results: One hundred and thirty-five CRC and 30 PDAC cases with 198 total cfDNA assays met criteria. Greatest non-RAS/RAF dominant gene MAF of 0.34% provided maximum discrimination for predicting RAS/RAF SNV detection. Sensitivity for RAS/RAF SNVs increased with dominant gene MAF, with MAF ≥1% predicting sensitivity >98%, MAF between 0.34 and 1% predicting sensitivity of 84.0%, and MAF £0.34% predicting sensitivity of 50%. For 43 cfDNA assays that did not detect RAS/RAF SNVs, 18 assays detected 34 other oncogenic variants, of which 80.6% were not also detected on tissue. Conclusions: Non-RAS/RAF dominant oncogenic mutation MAF ≥1% on cfDNA NGS predicts high sensitivity to detect RAS/RAF oncogenic SNVs in CRC and PDAC. MAF £0.34% indicates an assay may not reliably detect RAS/RAF SNVs, despite detection on tissue testing. Most variants from assays that did not detect RAS/RAF had MAF <1% and were not detected on tissue, suggesting potential confounding. These data suggest a practical approach to determining cfDNA assay adequacy, with implications for guiding clinical decisions in CRC and PDAC.

COPD diagnosis is tightly linked to the fixed-ratio spirometry criteria of FEV1/FVC < 0.7. African-Americans are less often diagnosed with COPD. Compare COPD diagnosis by fixed-ratio with findings and outcomes by race. Genetic Epidemiology of COPD (COPDGene) (2007–present), cross-sectional comparing non-Hispanic white (NHW) and African-American (AA) participants for COPD diagnosis, manifestations, and outcomes. Multicenter, longitudinal US cohort study. Current or former smokers with ≥ 10-pack-year smoking history enrolled at 21 clinical centers including over-sampling of participants with known COPD and AA. Exclusions were pre-existing non-COPD lung disease, except for a history of asthma. Subject diagnosis by conventional criteria. Mortality, imaging, respiratory symptoms, function, and socioeconomic characteristics, including area deprivation index (ADI). Matched analysis (age, sex, and smoking status) of AA vs. NHW within participants without diagnosed COPD (GOLD 0; FEV1 ≥ 80

Purpose of Review We reviewed the exposure assessments of ambient air pollution used in studies of fertility, fecundability, and pregnancy loss. Recent Findings Comprehensive literature searches were performed in the PUBMED, Web of Science, and Scopus databases. Of 168 total studies, 45 met the eligibility criteria and were included in the review. We find that 69% of fertility and pregnancy loss studies have used one-dimensional proximity models or surface monitor data, while only 35% have used the improved models, such as land-use regression models (4%), dispersion/chemical transport models (11%), or fusion models (20%). No published studies have used personal air monitors. Summary While air pollution exposure models have vastly improved over the past decade from a simple, one-dimensional distance or air monitor data to models that incorporate physiochemical properties leading to better predictive accuracy, precision, and increased spatiotemporal variability and resolution, the fertility literature has yet to fully incorporate these new methods. We provide descriptions of each of these air pollution exposure models and assess the strengths and limitations of each model, while summarizing the findings of the literature on ambient air pollution and fertility that apply each method.

Background Autoimmune (AI) diseases appear to be a product of genetic predisposition and environmental triggers. Disruption of the skin barrier causes exacerbation of psoriasis/eczema. Oxidative stress is a mechanistic pathway for pathogenesis of the disease and is also a primary mechanism for the detrimental effects of air pollution. Methods We evaluated the association between autoimmune skin diseases (psoriasis or eczema) and air pollutant mixtures in 9060 subjects from the Personalized Environment and Genes Study (PEGS) cohort. Pollutant exposure data on six criteria air pollutants are publicly available from the Center for Air, Climate, and Energy Solutions and the Atmospheric Composition Analysis Group. For increased spatial resolution, we included spatially cumulative exposure to volatile organic compounds from sites in the United States Environmental Protection Agency Toxic Release Inventory and the density of major roads within a 5 km radius of a participant’s address from the United States Geological Survey. We applied logistic regression with quantile g-computation, adjusting for age, sex, diagnosis with an autoimmune disease in family or self, and smoking history to evaluate the relationship between self-reported diagnosis of an AI skin condition and air pollution mixtures. Results Only one air pollution variable, sulfate, was significant individually (OR = 1.06, p = 3.99E−2); however, the conditional odds ratio for the combined mixture components of PM 2.5 (black carbon, sulfate, sea salt, and soil), CO, SO 2 , benzene, toluene, and ethylbenzene is 1.10 ( p -value = 5.4E−3). Significance While the etiology of autoimmune skin disorders is not clear, this study provides evidence that air pollutants are associated with an increased prevalence of these disorders. The results provide further evidence of potential health impacts of air pollution exposures on life-altering diseases. Significance and impact statement The impact of air pollution on non-pulmonary and cardiovascular diseases is understudied and under-reported. We find that air pollution significantly increased the odds of psoriasis or eczema in our cohort and the magnitude is comparable to the risk associated with smoking exposure. Autoimmune diseases like psoriasis and eczema are likely impacted by air pollution, particularly complex mixtures and our study underscores the importance of quantifying air pollution-associated risks in autoimmune disease.

BACKGROUND AND AIM: Autoimmune (AI) diseases are thought to be a product of genetic predisposition and environmental triggers. Disruptions of the skin barrier cause exacerbations of psoriasis where oxidative stress represents a mechanistic pathway for the pathogenesis of the disease. Oxidative stress is also thought to be the primary mechanism for the detrimental effects of air pollution. METHODS: We evaluated the association between the prevalence of autoimmune skin diseases (psoriasis or eczema,) and mixtures of air pollutants including six criteria air pollutants and constituents of PM2.5 in the Personalized Environment and Genes Study (PEGS) cohort consisting of 9414 subjects centered in NC, USA. We utilized land-use regression (LUR) predictions from the Center for Air, Climate, and Energy Solutions (CACES) and the Atmospheric Composition Analysis Group (ACAG). For increased spatial resolution, we included cumulative exposure to volatile organic compounds (VOC) based on the sum of exponentially decaying contributions from the EPA Toxic Release Inventory and the density of major roads within a 5km radius of a participant's address. We will use logistic regression with quantile g-computation, adjusting for age, gender, income, and smoking history to evaluate the relationship between self-reported diagnosis of an AI skin condition and mean air pollution mixtures from 2000-2016. RESULTS:The PEGS cohort reported a high prevalence of autoimmune diseases with 3177 (33.7%) reporting 1+ AI disease. In our specific outcomes of interest, 1173 (12.5%) reported psoriasis (398) and/or eczema (873). Preliminary results for PM2.5 composition show that the mixture components of sulfate, black carbon, and nitrate contribute to a positive overall conditional odds ratio for risk of AI skin disease. CONCLUSIONS:Using publicly available LUR air pollution data joined with the PEGS cohort, we elucidate the potential important components of particulate exposure on AI skin disease. KEYWORDS: mixtures, air pollution, autoimmune disease, LUR,

Nontuberculous mycobacteria (NTM) are environmental organisms that can cause opportunistic pulmonary disease with species diversity showing significant regional variation. In the United States, Hawai’i shows the highest rate of NTM pulmonary disease. The need for improved understanding of NTM reservoirs led us to identify NTM from patient respiratory specimens and compare NTM diversity between outdoor and indoor locations in Hawai’i. A total of 545 water biofilm samples were collected from 357 unique locations across Kaua’i (n = 51), O’ahu (n = 202), Maui (n = 159), and Hawai’i Island (n = 133) and divided into outdoor (n = 179) or indoor (n = 366) categories. rpoB sequence analysis was used to determine NTM species and predictive modeling applied to develop NTM risk maps based on geographic characteristics between environments. M. chimaera was frequently identified from respiratory and environmental samples followed by M. chelonae and M. abscessus; yet significantly less NTM were consistently recovered from outdoor compared to indoor biofilms, as exemplified by showerhead biofilm samples. While the frequency of M. chimaera recovery was comparable between outdoor and indoor showerhead biofilms, phylogenetic analyses demonstrate similar rpoB gene sequences between all showerhead and respiratory M. chimaera isolates, supporting outdoor and indoor environments as possible sources for pulmonary M. chimaera infections.