Citations

Abstract Rationale Extracorporeal membrane oxygenation (ECMO) is an increasingly utilized form of life support for patients with cardiac and/or respiratory failure. Fungal infections remain a serious challenge in patients supported by ECMO, with an estimated prevalence of up to 10% and high morbidity and mortality. While routine antifungal prophylaxis is uncommon in ECMO centers and widely debated, its impact on incidence, pathogenic organisms, resistance patterns, and outcomes has not been described. Methods This was a ten-year experience study of fungemia in patients receiving ECMO where most patients received antifungal prophylaxis. Institutional protocol was to prescribe prophylactic fluconazole based on risk stratification, substituted with echinocandins if indicated. Adults (18 years and older) with ECMO runs between 2014-2024 were screened for fungal organism growth on culture, then narrowed to those with positive blood cultures drawn in the window from 24 hours after cannulation through 72 hours after decannulation. Clinical, microbiological, and outcomes data were descriptively summarized. Institutional review board approved with a waiver of informed consent. Results Among 1,039 adult ECMO runs (979 patients), thirteen patients with fungemia were identified for a calculated incidence rate of 1.29 per 1000 ECMO days (95% CI 0.75 to 2.23). Twelve patients (92%) received antifungal prophylaxis; 85% had echinocandin and 38% azole exposure, with some overlap. Median duration of antifungal exposure was 14 days prior to positive culture. Seven patients (54%) had an open sternum at the time of ECMO cannulation, while 11 (85%) had femoral ECMO access. Four patients (31%) had Candida species isolated from other sources prior to fungemia (mediastinum and respiratory system). Candida parapsilosis (31%), C. albicans (23%), and C. guilliermondii (15%) were the most common isolates. The most likely sources were vascular access catheters (38%) and mediastinum (31%). Seven patients (54%) had suspected or confirmed seeding of ECMO hardware after positive blood cultures, though only two circuit exchanges were performed. Four patients (31%) showed evidence of non-susceptibility to their prophylactic antifungal class (Table 1), with a median 35-day exposure prior to positivity among those patients. Only 62% of patients demonstrated blood culture clearance (median 3 [IQR 2.5-7.75] days). Nearly all patients (92%) died within the hospital stay, including all patients with resistant organisms. Conclusions In an ECMO center with routine antifungal prophylaxis practices, the rate of fungemia identified during ECMO support was low. When fungemia developed, there was a high proportion of drug resistance and mortality. This abstract is funded by: None

Abstract Rationale Rural populations in the US experience a higher lung cancer burden compared to urban residents, potentially due to differences in risk factors and access to preventative care and early detection. We sought to characterize tobacco use, smoking cessation, and lung cancer screening patterns by rurality to identify modifiable gaps in the lung cancer care continuum. Methods We analyzed data from current and former smoking adults in the Southern Community Cohort Study, a large prospective cohort recruited from community health centers across 12 southeastern states. Participants aged 65-80 years with at least 9 months of Medicare Part A/B and less than 3 months of Part C coverage between 2014 and 2020 were included. Data were linked with the National Death Index and Medicare claims for outcome ascertainment. Rurality was defined using Rural-Urban Commuting Area (RUCA) codes. We compared demographic characteristics, smoking patterns, use of smoking cessation interventions, and receipt of low-dose computed tomography (LDCT) screening between rural and urban participants over time. Results Among 10,114 adults included (56% urban; 46% rural), 54% were female, 55% identified as Black/African American, about a third reported less than a high school education, and 45% lived in areas in the highest quartile of deprivation. Urban residents were of similar age (66 vs 67 years), and more likely to currently smoke (42% vs 35%), but had fewer baseline smoking pack-years (27 vs 30 pack-years) than rural residents. Approximately 2% died of lung cancer during follow-up. Using the USPSTF 2013 lung cancer screening criteria, 27% of urban and 26% of rural residents were eligible. This increased unevenly to 38% urban and 35% rural under the USPSTF 2021 criteria. LDCT uptake was low, increasing from 0% in 2014 to 6% in 2020 among screening-eligible participants. Use of cessation interventions was similarly low. Among current smoking participants, 7% received smoking cessation counseling, and 3% had a varenicline prescription. These patterns remained relatively stable over time, with no significant rural-urban differences in LDCT and cessation intervention use. Conclusion Despite modest differences in smoking prevalence and screening eligibility, we found comparable lung cancer mortality and similarly low utilization of LDCT and cessation interventions among rural and urban residents. Our findings suggest that, among people in lower socioeconomic groups, shared socioeconomic constraints may extend beyond the rural-urban divide. Further research is needed to understand how social determinants of health may be addressed to improve lung cancer outcomes across the screening continuum. This abstract is funded by: NIH

Abstract Background Sulfhemoglobinemia is a rare but potentially life-threatening dyshemoglobinemia resulting from the irreversible incorporation of sulfur into the heme moiety, producing hemoglobin species incapable of oxygen transport. Its clinical presentation often mimics methemoglobinemia, with cyanosis and oxygen saturation (SpO2) readings discordant from arterial partial pressure of oxygen (PaO2). Phenazopyridine, an over-the-counter urinary analgesic, has been implicated as a rare cause, in 3 previously documented cases. Prompt recognition is essential to avoid inappropriate therapy, particularly methylene blue, which can precipitate hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Case Presentation A 71-year-old man with Parkinson’s disease, Crohn’s disease, and chronic anemia presented with unexplained cyanosis and SpO2 readings in the 70-80% range, despite a normal PaO2 of 180 mmHg and absence of respiratory symptoms. He had self-initiated phenazopyridine for dysuria three days prior. CT angiography of the chest and echocardiography with bubble study were unremarkable. Attempts to quantify methemoglobin and carboxyhemoglobin were unsuccessful due to analyzer errors. Laboratory evaluation revealed acute anemia (hemoglobin 5.7 g/dL), indirect hyperbilirubinemia, and low haptoglobin consistent with hemolysis. He was managed supportively with high-flow oxygen, and transfusion of two packed red blood cell units. Although initial G6PD levels were normal, testing during hemolysis can yield false negatives. Given this and the risk of methylene blue-induced oxidative stress, conservative management with ascorbic acid was chosen. The patient’s SpO2 improved gradually, and he was discharged on hospital day three. Send-out tests later confirmed sulfhemoglobinemia (1.1%), elevated cytochrome b5 reductase activity, and normal methemoglobin. Discussion This case underscores the diagnostic and therapeutic challenge of differentiating sulfhemoglobinemia from methemoglobinemia. Both disorders produce functional hypoxia with SpO2-PaO2 dissociation, but sulfhemoglobin cannot revert to hemoglobin and requires erythrocyte turnover for resolution. While methylene blue is the standard therapy for methemoglobinemia, it is ineffective for sulfhemoglobinemia and contraindicated in G6PD deficiency. In our patient, supportive care and transfusion facilitated recovery. Using the Naranjo Adverse Drug Reaction Probability Scale, the causality score was 7, indicating a highly probable relationship between phenazopyridine exposure and sulfhemoglobinemia. A high index of suspicion for G6PD deficiency as well as dyshemoglobinemia with a multidisciplinary collaboration are essential for diagnosis and management of unexplained cyanosis. This abstract is funded by: None

Abstract Rationale Thymic stromal lymphopoietin (TSLP) is an epithelial alarmin chiefly implicated in T2 airway inflammation, though it may also participate in broader (non-T2) inflammatory processes. The utility of airway epithelial gene expression of TSLP and its specific receptor subunit, cytokine receptor-like factor 2 (CRLF2), as biomarkers of downstream inflammation and clinical outcomes remains unclear. Methods We analyzed RNA sequencing data from bronchial airway brushing obtained in phase 1 of the SPIROMICS bronchoscopy sub-study (N = 161: 23 never-smokers, 67 ever-smokers with COPD, 71 ever-smokers without COPD). We related airway TSLP and CRLF2 expression to clinical, hematologic/sputum measures, and gene-expression signatures of T2/eosinophilic and neutrophilic inflammation, including to our published T2 signature and to eosinophil and neutrophil signatures derived from single-cell atlas data. Associations used Spearman correlations and linear models adjusted for age, sex, race/ethnicity, COPD status, smoking status, and pack-years. Results CRLF2 expression correlated with gene-expression evidence of both T2/eosinophilic and neutrophilic inflammation: T2 signature (ρ = 0.26, p < 0.001), eosinophil signature (ρ = 0.44, p < 0.001), and neutrophil signature (ρ = 0.39, p < 0.001). CRLF2 was positively associated with log sputum neutrophil count (ρ = 0.24, p = 0.024) and blood neutrophil count (ρ = 0.036, p < 0.001), but not with sputum or blood eosinophil counts. Higher CRLF2 related to worse baseline lung function, particularly among current smokers, (lower post-bronchodilator FEV1: ρ = −0.21, p = 0.008), as well as greater 5-year FEV1 decline across current and former smokers (ρ = −0.22, p = 0.007). Significant findings persisted after covariate adjustment. In contrast, TSLP expression, although strongly correlated with expression of the epithelial alarmin IL33 (ρ = 0.53, p < 0.001), was negatively correlated with CRLF2 (ρ = −0.24, p = 0.002) and with eosinophil and neutrophil gene-expression signatures (ρ = −0.26 and −0.33, both p < 0.001). TSLP expression showed no association with sputum or blood cell counts. Conclusions In bronchial epithelium from SPIROMICS, gene expression of CRLF2, but not of TSLP, tracked with downstream alarmin-relevant inflammatory programs, consistent with a regulatory role in TSLP signaling through TSLPR, as well as with clinically meaningful outcomes. CRLF2 expression was associated with evidence of both T2/eosinophilic and neutrophilic inflammation, and with lower baseline FEV1 and accelerated FEV1 decline, suggesting engagement of a broader, clinically relevant inflammatory milieu. By contrast, epithelial TSLP transcript levels mirrored IL33 gene expression but were not associated with cellular or transcriptomic inflammation. These findings position CRLF2, rather than TSLP expression itself, as a potential airway biomarker of TSLP-axis activity and disease impact with potential implications for patient stratification as well as strategic approaches for TSLP-pathway-targeted therapies. This abstract is funded by: SPIROMICS was supported by contracts from the NIH/NHLBI (HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C, HHSN268200900020C, 75N92024D00012), grants from the NIH/NHLBI (U01HL137880, U24HL141762, R01HL182622, R01HL144718, and R01HL093081), and supplemented by contributions made through the Foundation for the NIH and the COPD Foundation from Amgen; AstraZeneca/MedImmune; Bayer; Bellerophon Therapeutics; Boehringer-Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Chiesi Farmaceutici S.p.A.; Forest Research Institute, Inc.; Genentech; GlaxoSmithKline; Grifols Therapeutics, Inc.; Ikaria, Inc.; MGC Diagnostics; Novartis Pharmaceuticals Corporation; Nycomed GmbH; Polarean; ProterixBio; Regeneron Pharmaceuticals, Inc.; Sanofi; Sunovion; Takeda Pharmaceutical Company; Theravance Biopharma; Verona; and Mylan/Viatris.

Abstract Rationale Alpha-1 antitrypsin deficiency (AATD) continues to be underdiagnosed. The estimated prevalence of the most common severe deficient genotype, PI*ZZ, is ∼1:3500 or 100,000 Americans but only ∼10,000 such individuals have been recognized. Diagnostic delays persist and these delays are associated with worse disease. High-resolution CT (HRCT) imaging may contain latent phenotypic AATD signatures that are not visibly apparent to clinicians. We hypothesized a deep learning model could identify imaging patterns predictive of AATD from inspiratory HRCT scans. Methods Confirmed genotypes and HRCT scans were pooled from COPDGene, SPIROMICS, and GRADS, yielding 350 MM, 102 MZ, and 69 ZZ participants. Only scans reconstructed with smooth kernels (GE STANDARD, Philips B, Siemens B31f/B35f) and slice thickness < =1.25mm were used. The cohort was selected to have similar distributions of quantitative emphysema, sex, and age by matching five MZ and two MM subjects to each ZZ subject (<10-year age difference, same sex, and <3% difference in %LAA). Tobacco smoke-exposure was more prevalent among the MM/MZ groups given these were predominantly from the tobacco smoke-enriched COPDGene and SPIROMICS cohorts. A DenseNet121 convolutional neural network (CNN) was trained using the MONAI platform to predict genotype by outputting probabilities for MM, MZ, and ZZ. Input to the CNN was a three-channel LAA-910, LAA-950, and LAA-970 map downsampled to 2.0mm3 resolution to remove bias due to differences in scanner and image reconstruction parameters. Five-fold cross-validation was performed. Area under the curve (AUC) was calculated for classification of ZZ vs other genotypes (MM/MZ) and MZ vs MM, with statistical significance assessed at p < 0.05. Results The three groups were similar across age (mean±SD years: MM 57.9±8.8, MZ: 57.5±8.9, ZZ: 55.0±10.7), sex (% female: MM: 48.2%, MZ: 46.7%, ZZ: 47.6), and emphysema (LAA-950%: MM: 13.0±12.2, MZ: 12.4±11.8, ZZ: 13.1±11.9). There was a higher prevalence of ever smokers among MM (100%) and MZ (91.7%), compared to ZZ (47.6%). The model achieved an AUC of 0.806 (p < 0.001) for classification of ZZ vs other genotypes, demonstrating robust discriminatory ability for homozygous AATD. Classification of MZ vs other genotypes did not achieve an AUC significantly greater than 0.5. Conclusions This proof-of-concept study demonstrates that deep learning applied to routine inspiratory HRCT can accurately identify homozygous AATD. These findings support the potential role of imaging-based machine learning as a non-invasive screening tool for undiagnosed ZZ individuals. Future work will focus on cohort enrichment, integration with clinical parameters, and explainability of model-derived imaging features. This abstract is funded by: NIH NHLBI K23HL173570

Abstract Introduction Bronchiectasis is a chronic respiratory disease that increases fatigue, disability, and impairs quality of life. However, the impact of fatigue on patients with bronchiectasis, even in short-term follow-up, has not been sufficiently examined. We explored the association between fatigue and clinical outcomes among patients with bronchiectasis. Methods Adult bronchiectasis patients enrolled in the US Bronchiectasis and Nontuberculous Mycobacteria Research Registry were retrospectively analyzed. Patients with at least one annual follow-up visit in the 3-5 years post baseline and with fatigue data at both baseline and follow-up were included. Patients were grouped as experiencing fatigue versus not experiencing fatigue in the 2-years prior to baseline as reported at their baseline visit. We explored the relationship between baseline fatigue with patient demographics, co-existing conditions, components of the modified bronchiectasis severity index at baseline and follow-up. Wilcoxon, chi-square, and Fisher’s exact tests were used to assess the differences in continuous variables and associations between categorical variables, respectively. Stepwise multivariable logistic regression models explored the relationship of baseline fatigue with exacerbations and hospitalizations at follow-up. Model selection predictors were evaluated based on clinical relevance or p < 0.05 in univariable analyses. Results 1265 adults with bronchiectasis met the inclusion criteria. 563(45%) reported experiencing fatigue and 702 (55%) did not. The median age (interquartile range) was 70(62-78) years and patients were predominantly female (n = 1042, 83%). At baseline, patients experiencing fatigue had a higher proportion of co-existing diagnoses such as gastroesophageal reflux disease, chronic obstructive pulmonary disease, and rheumatologic disease, compared to those without fatigue (all p < 0.05). Furthermore, patients with fatigue had a higher prevalence of pulmonary-related hospitalizations (p < 0.001) at baseline and follow-up. Pseudomonas aeruginosa colonization and elevated dyspnea (modified Medical Research Council [mMRC] grade≥1) were more prevalent among those experiencing baseline fatigue compared to those without (all, p < 0.05). History of prior exacerbations (Odds Ratio [OR]:1.67, 95% CI:1.17-2.41) and baseline Pseudomonas aeruginosa colonization (OR:1.22, 95% CI:1.01-1.47) were significantly associated with increased odds of exacerbations at follow-up. In multivariable stepwise logistic regression, there was an increased odds of at least 1-hospitalization at follow-up among males (OR:2.23, 95% CI 1.12-4.42), patients with decreased Body Mass Index (OR:0.93, 95% CI: 0.87-1.0), and among patients with elevated dyspnea (mMRC grade ≥1) at baseline (OR:2.22, 95% CI: 1.16-4.24),[Table 1]. Conclusions Fatigue in bronchiectasis patients is associated with a more severe disease and greater healthcare utilization, although it may not independently predict future exacerbations or hospitalizations when accounting for other factors. This abstract is funded by: Bronchiectasis and NTM Association

Abstract Rationale The United States has the highest per capita incarceration rate of any developed democracy. As the incarcerated population ages, medically complex and frail patients are increasingly hospitalized in the community, often arriving without decisional capacity and with limited family involvement. This is the first analysis of state laws and policies governing decision-making for incapacitated incarcerated patients. Methods Two team members independently conducted Westlaw and Internet searches for statutes, regulations and department of corrections (DOC) policies from 50 states and the District of Columbia, identifying language about medical decision-making for incapacitated incarcerated patients. These parallel searches were merged into a single database and reviewed by the analytic team, who created a codebook of inductively and deductively derived themes, guided by principles of grounded theory. The codebook was then systematically applied to the database by 2 independent coders; all data were double-coded. Disputes were resolved by consensus with the entire analytic team, in consultation with a legal scholar. Results Thirty-four of 51 jurisdictions have language addressing decision-making for incapacitated incarcerated patients. Data collected include the definition and determination of incapacity, language affirming incarcerated persons’ right to autonomy in medical decision-making, approaches to decision-making for patients with and without surrogate decision-makers, and whether treatment over patient/surrogate objection is authorized. Assertions about the importance of advance care planning (n = 25) are often undercut by procedural hurdles (n = 20), such as complex witnessing requirements for advance directive completion. Many jurisdictions (n = 26) allow family or friends to serve as legally recognized decision-makers. Thirteen jurisdictions exclude an incarcerated person from serving as decision-maker for another incarcerated person. Fourteen jurisdictions have provisions allowing for treatment over the objection of a patient or their surrogate. While approaches to unrepresented patients differ widely (Figure), 5 jurisdictions grant narrow decisional authority to treating physicians and 4 jurisdictions authorize correctional employees to make medical decisions. Conclusion A heterogeneous assortment of laws, policies and regulations govern the care of incapacitated incarcerated patients, with wide variation observed from jurisdiction to jurisdiction. One-third of jurisdictions lack policies or language regarding decision-making processes for incapacitated incarcerated patients. Even more troubling, 14 jurisdictions allow treatment over a patient or surrogate’s objection and 4 jurisdictions delegate authority over decisions for unrepresented patients to correctional employees, such as the prison medical director or the warden. These findings raise serious concerns about autonomy, beneficence and justice. National reform is needed to align correctional policies with established ethical standards for surrogate decision-making. This abstract is funded by: National Institute on Aging

Abstract Introduction The COVID-19 pandemic exposed underrecognized structural deficiencies in pandemic preparedness across the US, particularly impacting marginalized and medically vulnerable populations. State leaders who were developing policies to allocate critical care resources, often called crisis standards of care (CSC), confronted challenges such as whether and how to incorporate age and chronic conditions into triage protocols, how to contend with imperfect illness acuity scores such as the sequential organ failure assessment (SOFA), and whether essential worker status or area deprivation index (ADI) ought to confer an advantage during triage. To our knowledge, this is the first analysis to highlight CSC writers’ approach to ethical challenges, including from states whose policies provoked corrective action from the Office of Civil Rights (OCR). This study explores how state leaders navigated ethical controversies underlying states’ CSC policies, including whether those controversies were satisfactorily resolved. Methods Between February-September 2022 we conducted semi-structured interviews of public health leaders tasked with developing their states’ (CSC) policies. Interviews were transcribed verbatim and a codebook was developed iteratively, using inductively and deductively derived themes based on principles of grounded theory. The codebook was systematically applied to transcripts; disputes were resolved by consensus discussion among analytic team members. Results Leaders from 34 states were interviewed. Participants described how their states’ CSC policy writing committees considered the role of age in triage, some proposing age as a tiebreaker, or considering age only if coupled with measures of frailty or chronic illness, with others proposing age as an “exclusion criterion.” Many leaders acknowledged a controversial approach to disability in early versions of their policies, some describing how they responded to civil rights complaints. Participants described debates over whether pandemic triage decisions should advantage patients from underserved populations or affirmatively consider essential worker status or pregnancy. While most leaders regretted that early iterations of their policies stood to exacerbate health disparities, others described a less conciliatory response to civil rights complaints. In particular, triage exclusion criteria, whereby certain patients would be excluded outright from certain resources, provoked intense debate. Conclusion We describe ethical controversies that stymied CSC policy writing committees during the COVID-19 pandemic. Leaders described spirited debate around how age, disability, and justice ought to factor into triage; few described satisfactory resolution to those debates. Improved community engagement and adherence to civil rights protections in CSC are imperative to protect marginalized populations as we prepare for future calamites, whether global or local. This abstract is funded by: R03 AG73987; K76 AG88403

Abstract Introduction Burkholderia, Achromobacter, and Stenotrophomonas species are associated with worse clinical outcomes in cystic fibrosis (CF),1 though little is known about their prevalence or pathogenicity in non-CF bronchiectasis (pwBE). Herein we describe the prevalence and clinical characteristics of pwBE who isolated each of these three organisms. Methods We conducted a retrospective cross-sectional analysis of baseline data from the US Bronchiectasis and Nontuberculous Mycobacteria (NTM) Research Registry (BRR). Adult bronchiectasis patients with known Achromobacter, Burkholderia cepacia complex (BCC), or Stenotrphomonas maltophilia culture results were included. Patients were stratified according to the presence of at least one positive culture among the gram-negative species. Demographics, clinical characteristics, and first annual follow-up culture results were summarized descriptively for the overall study population and between groups. No inferential analyses or hypothesis testing was performed. Results 5003 pwBE met the inclusion criteria, of which 39 (0.78%) isolated Achromobacter species, 11 isolated Burkholderia (0.22%), and 288 isolated Stenotrophomonas maltophilia (5.8%). Patients with Achromobacter were older, with a median age (interquartile range) of 76 (73.0-79.0) years, compared to the overall bronchiectasis cohort (69.0 years). Those with Burkholderia or Stenotrophomonas were younger, at 69.0 (53.0-75.0) and 71.0 (63.0-77.0) years, respectively. A high proportion of those with Achromobacter were male (31%) versus those with Burkholderia (9%) and Stenotrophomonas (24%), were current or former smokers (46%), were more likely to have had one or more exacerbations in the 2 years prior to enrollment (87%) than the overall BE cohort (57%), and were more likely to have had pulmonary-related hospitalization than those with either Burkholderia or Stenotrophomonas (46% vs. 27% and 19%, respectively). PwBE who isolated Burkholderia were less likely to have co-colonization with Pseudomonas aeruginosa or NTM species (9% each). At first annual follow-up, no patients with baseline Burkholderia isolated them at follow-up, and only 31% with baseline Stenotrophomonas isolated it at follow-up. Conclusion Overall prevalence of Achromobacter, Burkholderia, and Stenotrophomonas species in the BE cohort was low. Patients who isolated Achromobacter species were older, more likely to be current or former smokers, and more likely to experience pulmonary exacerbation and hospitalization. 15 patients who had not previously isolated Achromobacter, and 3 patients who had not previously isolated Burkholderia did so at annual follow-up. Interestingly, no patients with baseline Burkholderia isolates went on to isolate it at annual follow-up, which contradicts earlier studies in pwCF.2 The number of patients isolating Burkholderia in the U.S. BRR is very low, thereby limiting interpretation. This abstract is funded by: None

Abstract Rationale Gastroesophageal reflux disease (GERD) is a common comorbidity in non-cystic fibrosis bronchiectasis (NCFB), yet its impact on clinical outcomes remains poorly defined. We sought to determine whether GERD is associated with worse clinical outcomes in patients with NCFB using a large, real-world database. Methods We conducted a retrospective cohort study using the TriNetX platform, identifying patients with NCFB (ICD-10 J47*) with and without concurrent GERD (ICD-10 K21*), excluding those with cystic fibrosis (ICD-10 E84*). Propensity score matching (PSM) was performed using 1:1 nearest neighbor matching without replacement, controlling for age, sex, race/ethnicity, obesity, socioeconomic risk factors, and tobacco use. Primary outcomes included pneumonia, bronchiectasis exacerbations, intensive care unit admission, mechanical ventilation, and mortality. Statistical analyses included risk ratios and Cox proportional hazards modeling for survival outcomes. Results Out of 421,710 patients with NCFB in the dataset from January 2000 to September 2025, 186,874 (44%) had a diagnosis of GERD. After propensity score matching, 179,753 patients with NCFB+GERD and 179,753 patients with NCFB-only were included (mean age 74.0±13.1 years, 58.8% female, 67.1% White). Baseline characteristics were well-balanced after matching. Median follow-up was approximately 2.5 years for both cohorts (898 vs 889 days; similar means and IQR), ensuring balanced observation time. Compared to NCFB-only, NCFB+GERD was associated with increased risks for mortality (risk ratio 1.04, 95% CI 1.02-1.05; p < 0.001), pneumonia (risk ratio 1.06, 95% CI 1.05-1.08; p < 0.001), bronchiectasis exacerbations (risk ratio 1.03, 95% CI 1.01-1.06; p = 0.006), and mechanical ventilation (risk ratio 1.14, 95% CI 1.10-1.18; p < 0.001). Intensive care unit admission rates were comparable between groups (risk ratio 1.00; p = 0.65). Conclusions In this large propensity score-matched analysis, concurrent GERD in NCFB is independently associated with increased mortality, pneumonia, bronchiectasis exacerbations, and mechanical ventilation requirements. These findings suggest GERD may represent a modifiable risk factor warranting aggressive management in NCFB patients. Study limitations include retrospective design, reliance on ICD-10 coding accuracy, and potential unmeasured confounders. Our results support systematic screening and treatment of GERD in NCFB, but whether targeted GERD management can modify the natural history of NCFB future investigation. This abstract is funded by: None