Citations

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

Abstract Background Sputum color is a visual marker of airway inflammation and disease activity in bronchiectasis, ranging from clear or light gray (mucoid) to yellow-green (purulent), the latter largely reflecting neutrophil myeloperoxidase release. This study evaluated associations between sputum color and common clinical markers of disease activity to determine which parameters differed most between color categories. Methods Forty spontaneous sputum samples were analyzed from 80 consecutive adults with non-cystic fibrosis bronchiectasis (median age 70 years [IQR 12]; 74% female) enrolled between January 2024 and April 2025 in an observational study. Sputum color was graded using the Murray Sputum Color Chart and classified as mucoid (color #1) or purulent (colors #2-4). Clinical parameters, including blood cell counts, C-reactive protein (CRP), fractional exhaled nitric oxide (FeNO), and results of bacterial and acid-fast bacillus cultures (induced or bronchoscopic), were obtained from medical records if available within one month of enrollment. Categorical variables were analyzed using chi-square or Fisher’s exact tests and continuous variables with the Mann-Whitney U test. A secondary analysis compared patients who could versus could not produce spontaneous sputum. Results Of 40 samples, 20 (50%) were purulent. Blood neutrophil counts (median 4.5 vs. 3.9 x109/L), neutrophil-to-lymphocyte ratios (2.5 vs. 2.6), and eosinophil counts (1.7 vs. 1.7 x109/L) did not differ significantly between groups (n = 26). FeNO was normal in all 10 patients with available data and was not analyzed further. CRP was higher among patients with purulent sputum (4.6 vs. <3 mg/L; n = 20; p = 0.044). Bacterial growth was more frequent in purulent than mucoid samples (73% vs. 31%; n = 31; p = 0.032). Isolates in the purulent group included Klebsiella, Pseudomonas, Staphylococcus, and Streptococcus (n = 2 each), and single isolates of Acetobacter, Acinetobacter, Chryseobacterium, Delftia, Enterobacter, Escherichia, and Moraxella. In the mucoid group, Pseudomonas, Staphylococcus (n = 2 each), and Stenotrophomonas (n = 1) were identified. Mycobacterial growth did not differ significantly (20% vs. 12.5%; n = 31; p = 0.65). Patients unable to produce spontaneous sputum had a higher rate of mycobacterial isolation on induced/bronchoscopic samples (43% vs. 16%; n = 54; p = 0.027), though other parameters were similar. Over 90% of measurements were obtained within three days of enrollment, and freezing did not appear to alter sputum color. Conclusions Even within a small cohort, purulent sputum was associated with higher CRP and greater bacterial growth, supporting sputum color as a rapid, inexpensive marker of disease activity in bronchiectasis. Further research should clarify whether sputum color primarily reflects bacterial colonization, airway inflammation, or both. This abstract is funded by: None

Abstract Rationale Glucagon-like peptide 1 (GLP-1) receptor agonists are novel antihyperglycemic drugs that have shown benefit in various disease states, namely in cardiovascular and renal disease. GLP-1 agonists in murine models of obstructive lung diseases have been shown to decrease airway inflammation and hyperresponsiveness. In humans, some observational studies show an association between GLP-1 agonist use and reduced exacerbations of chronic obstructive pulmonary disease (COPD). In a meta-analysis, GLP-1 agonist use decreased the risk of several respiratory disorders including bronchitis (3). Bronchiectasis is another chronic airway disease, characterized by abnormal airway dilation leading to impaired mucous clearance and increased risk of infection (4). Data on the association between GLP-1 agonist use and bronchiectasis is sparce. We, therefore, examined the effects of GLP-1 agonists on the mortality of patients with bronchiectasis in a large sample size. Methods In this retrospective case control study, we identified patients with bronchiectasis from a single-center database of patients at our institution. We identified patients with bronchiectasis who received a GLP-1 agonist and compared them to patients who never received a GLP-1 agonist. Data was displayed as median with interquartile range and a Kaplan-Meier curve was used for mortality analysis. Results We identified a total of 256,777 patients with bronchiectasis. Of these, 249911 patients with bronchiectasis had not received a GLP-1 agonist and 6866 patients had received a GLP-1 agonist. The median age for patients in the GLP-1 group was 63 vs. 64 for the control group. 54.5 % of patients in the GLP-1 group were female compared to 52.9% in the control. Patients who received a GLP-1 agonist had improved survival at 1 month (99.9% for the GLP-1 group vs. 98.7% for the control group), 5 months (98.9% for the GLP-1 group vs. 95.9% for the control group), 10 months (97.9% for the GLP-1 group vs. 93.5% for the control group), 30 months (91.9% for the GLP-1 group vs. 86.8% for the control group) and 60 months (81.8% for the GLP-1 group vs. 79.3% for the control group), p < 0.001, Hazard ratio 0.56 (95% CI 0.50 - 0.62). Conclusion Our study showed that GLP-1 agonists are associated with improved survival in patients with bronchiectasis. Several mechanisms may contribute to this effect, including weight loss and reduction of cardiovascular mortality. Further studies are needed to investigate GLP-1 agonists as a potential therapeutic option for bronchiectasis, and to elucidate the mechanisms behind this association. This abstract is funded by: none

Abstract Rationale Bronchopulmonary dysplasia (BPD) is a chronic lung disease that significantly affects premature infants, leading to impaired lung development, inflammation, and fibrosis due to sustained exposure to high oxygen levels in the Neonatal Intensive Care Unit (NICU). In BPD, airway narrowing and hyperreactivity are common, making bronchodilation beneficial. Caffeine, a respiratory stimulant typically used for apnea of prematurity, also has bronchodilatory properties. This study investigates caffeine’s impact on airway remodeling (fibrosis and cellular proliferation) in fetal airway smooth muscle cells (fASMs) exposed to mild hyperoxic stress. By inhibiting phosphodiesterase, caffeine increases cyclic adenosine monophosphate (cAMP) levels, thereby relaxing airway smooth muscle. Caffeine’s influence on calcium (Ca2+) kinetics is essential for muscle contraction and relaxation. The goal is to better understand caffeine’s therapeutic role in bronchodilation and reducing fibrosis and proliferation in BPD. Methods Ca2+ imaging, proliferation assay, and immunofluorescence imaging (IF) were performed. fASMs were exposed to normoxia (21% O2) or mild hyperoxia (∼40% O2) for 48 hours, with or without caffeine treatment. Results Acute caffeine exposure (25 mM) decreased Ca2+ amplitude (corresponding to a dilatory effect) after addition of acetylcholine (10 μM) in normoxia. Caffeine treatment reduced cell proliferation in both normoxic and hyperoxic groups. Caffeine decreased both Ki67 (marker of proliferation) and Col1a1 (marker of fibrosis) protein expression under hyperoxic conditions. Conclusions Caffeine influences Ca2+ signaling, reduces cell proliferation and fibrosis, and, thus, may modulate airway remodeling and hyperreactivity under hyperoxic stress, suggesting its potential as a therapeutic strategy for BPD. This abstract is funded by: NIH R01 HL56470, R01 HL177837

Abstract Rationale Long COVID (LC) has affected approximately 400 million people worldwide, with about 20 million in the US. LC is characterized by a host of new symptoms, including neuropsychiatric disorders including cognitive impairment. Disruption of the gut microbiome has been correlated with symptoms of LC. This study examined whether gut microbiome modulation via intake of probiotic fermented foods mitigated psychiatric and cognitive impairments. Methods This was a pilot trial performed at a single academic medical center that enrolled and randomized patients with LC 1:1 into the treatment vs. control arm. Those enrolled into the treatment arm received teaching on the gut microbiome, its relationship to LC, and were encouraged to eat a diet high in probiotic fermented foods for 12 weeks. Those in the control arm did not receive the teaching and were encouraged to eat their normal diet. Diets were tracked using the Mayo Clinic Diet application on a smart phone at least three days per week, and those in the treatment arm received routine calls to discuss protocol adherence and gather subjective feedback on the trial. Neuropsychiatric questionnaires (HADS, IES-R, EQ-5D-5L, and MoCA Blind) were completed at enrollment and upon completion of the trial. Questionnaire scores were evaluated for changes using a paired t-test, with statistical significance defined as a p-value <0.05. Correlation between the fermented food intake and improvements in questionnaires was completed using the Spearman test. Results 43 patients were enrolled; 18 patients in the treatment arm and 20 patients in the control arm completed the trial. Groups did not differ by age, race, education, or baseline neuropsychiatric testing. There was a significant increase in fermented food intake in the treatment arm over the duration of the study. Those in the treatment arm had improvements in questionnaires related to anxiety, PTSD, and quality of life. Those in the control arm only had improvements in reported overall quality of life. Intra-group changes can be seen in Table 1. Correlations between fermented food intake and change in questionnaire scoring showed numerical but not statistically significant improvements in many of the questionnaires, except for the MOCA questionnaire and EQ-5D-5L Self-Care question. Conclusion Implementing a diet high in fermented foods in patients with LC appears to have some signal for improvement in neuropsychiatric symptoms. Completing a larger trial would help clarify if changes would be statistically significant. This abstract is funded by: Mayo Clinic Critical Care Research Committee

Abstract Rationale Teaching invasive bedside procedures is a core responsibility of critical care physicians, yet few validated tools exist to evaluate teaching effectiveness in this high-stakes environment. Building on prior qualitative work identifying key traits and behaviors of effective IBP teachers, we aimed to develop and validate the Invasive Bedside Procedure Teacher Effectiveness Scale (IBP-TES) to advance assessment and faculty development in procedural education. Methods This multicenter validation study recruited internal medicine residents and PCCM fellows from two academic institutions (Oregon Health & Science University (OHSU) and Mayo Clinic) in which each learner reviewed two standardized videos of simulated ultrasound-guided central venous catheter insertions supervised by critical care physicians. Learners rated supervising teachers using the eight-item IBP-TES, derived from prior qualitative themes of effective procedural teaching. Factor analysis using generalized estimating equations accounted for repeated measures, and orthogonal rotation was applied for factor extraction. The number of factors retained was determined using the minimal proportion criterion and visual inspection of the scree plot. Cronbach’s α assessed internal consistency reliability. Analyses were performed in SAS v9.4. Results Thirty-eight learners (63% OHSU, 37% Mayo Clinic) completed 76 IBP-TES evaluations of supervising physicians. Factor analysis identified two underlying domains accounting for most of the variance: (1) Procedural Teaching Behaviors—pre-briefing, communication, feedback, environmental control, and procedural expertise (Cronbach’s α = 0.80); and (2) Interpersonal Traits—calmness, adaptability, and learner autonomy (α = 0.72). Overall reliability was strong (α = 0.80), and findings were consistent in sensitivity analyses unadjusted for repeated measures. These domains collectively reflect that effective IBP supervision integrates both structured teaching behaviors and interpersonal qualities that foster learner engagement and safety. No significant associations were observed between IBP-TES scores and learner demographics or postgraduate year. Conclusions The IBP-TES demonstrated strong internal consistency and a reproducible two-factor structure encompassing procedural teaching behaviors and interpersonal traits. This validated tool provides a structured framework for assessing procedural teaching effectiveness and guiding faculty development. Future work will evaluate its use in real-world ICU settings to further improve procedural supervision and patient safety. This abstract is funded by: None

Abstract Introduction Emergent endotracheal intubation in the intensive care unit (ICU) is a high-risk, time-sensitive procedure performed to maintain airway patency and ensure adequate oxygenation and ventilation, often complicated by hypotension, hypoxemia, or cardiac arrest. Successful outcomes depend on precise team coordination, communication, and situational awareness. Drawing inspiration from the demonstrated benefits of simulation-based cardiopulmonary resuscitation training in enhancing team performance, this study examines the feasibility of implementing in situ “mock intubation” in the ICU. The objective is to determine whether this approach can be seamlessly integrated into routine practice to improve teamwork, procedural readiness, and patient safety. Methodology A prospective interventional study was conducted in the medical ICU at Mayo Clinic Rochester over two months. ICU staff—including physicians, advanced practice providers (APP), nurses, and respiratory therapists—participated in eight scheduled 45-minute in situ mock intubation sessions integrated into routine clinical hours. Each session included five participants (one physician faculty, one physician trainee/APP, two nurses, and one respiratory therapist) and incorporated case-based scenarios requiring completion of the intubation and management of post-procedural complications. Structured debriefings followed each session to identify performance gaps, enhance team communication, and assess the educational value and feasibility of incorporating mock intubation into routine ICU practice. Results A total of eight mock intubations were conducted with 40 participants. Sessions were seamlessly integrated into the routine clinical workflow without disruption. Participants reported high satisfaction, unanimously agreeing that the sessions were valuable and should be continued. Feedback emphasized psychological safety and realism: “This offered a safe space to communicate,” one noted; another stated, “It’s important to practice where it’s easy to make mistakes,” and a third remarked, “Real-life experiences were brought into simulations.” These themes underscore participants’ desire for ongoing sessions and their perceived real-world relevance. Conclusion Mock intubation using in situ simulation provides a practical approach to training for emergent endotracheal intubation, enhancing team communication, coordination, and situational awareness in the ICU. This on-site format eliminates the need for off-unit scheduling and was well received by staff. The potential of in situ mock intubation to mirror the success of simulated cardiopulmonary resuscitation training highlights the importance of team-based procedural preparation in high-acuity environments. The intervention fosters procedural readiness, teamwork, and a culture of safety. Given its feasibility, clinical relevance, and positive reception, in situ mock intubation should be integrated into routine ICU practice as a team training tool for high-risk procedures. This abstract is funded by: None

Abstract Rationale Major advances in precision medicine and immunotherapy have led to improved outcomes for patients with metastatic cancer, but have also introduced new, severe toxicities that can necessitate ICU admission. The overall mortality remains substantial; however, prior studies have often been single centered with small sample sizes. Therefore, we sought to provide an overview of the current literature with pooled estimates of short- and long-term mortality. Methods This study was registered a priori on Open Science Framework (10.17605/OSF.IO/438RY) and conducted per the Cochrane Handbook. A medical librarian searched MEDLINE, Embase, PubMed, Cochrane Central Register for Controlled Trials, supplemented by hand searching. Eligible studies included randomized and observational designs with >10 patients; studies were included if ≥ 70% of participants had metastatic disease when subgroup data were unavailable. The primary outcome was ICU mortality. Other outcomes included hospital, 30-day, 3-month, 6-month, and 12-month mortality. Pooled prevalence and 95% CIs were estimated using a random-effects model with Freeman-Tukey transformation. Risk of bias was assessed using the validated 10-item tool for prevalence studies. Results Of 4752 unique citations, 49 were included (N = 168,209). All studies were rated as having low risk of bias with the main threat to external validity being single-center design. Fourteen studies were multi-centered and 3 were multi-national, with the rest being single center. Across 23 studies (N = 2,918), the ICU mortality was 32% (95% CI: 25-39%; I2 = 89%; Figure 1). Across 5 studies (N = 400) with a focus on lung cancer, there was significantly higher ICU mortality (53% [43-64%]; I2 = 75% versus 26% [20-34%]; I2 = 86%; PQ = <0.01). Among 5 studies (N = 474) focusing on acute respiratory failure (ARF), ICU mortality was numerically higher but not statistically significant (49% [33-66%]; I2 = 91% versus 26% [20-34%]; I2 = 85%; PQ=0.07). Hospital mortality was 50% (44-56%; I2 = 99%; N = 157,682), 30-day mortality was 48% (39-57%; I2 = 84%; N = 1,067), 3-month mortality was 69% (62-74%; I2 = 80%; N = 1,296), 6-month mortality was 70% (59-79%; I2 = 91%; N = 1,310), and 12-month mortality was 84% (71-91%; I2 = 95%; N = 1,446; Figure 1). Conclusions Among critically ill adults with metastatic cancer, about one-third died in the ICU, half survived to hospital discharge, and 12-month mortality was 84%. There was considerable heterogeneity in mortality estimates, with worse outcomes in lung cancer. Given that ICU admission criteria and illness severity may differ, large multi-center studies are needed to clarify temporal trends and identify management strategies to improve outcomes. This abstract is funded by: None

Abstract Introduction We report a case of an 87-year-old male presenting with debilitating fatigue and multifocal airspace opacities that improved with corticosteroid therapy, later diagnosed as VEXAS syndrome. Case Presentation An 87-year-old man with a history of atrial fibrillation (on Xarelto), diastolic heart failure, coronary artery disease, sick sinus syndrome status post pacemaker placement, hypertension, and chronic kidney disease presented with profound fatigue and failure to thrive over the last few months. A CT chest showed multifocal consolidative airspace opacities (Figure 1a) interpreted as “non-resolving pneumonia.” Despite multiple antibiotic courses, symptoms persisted. Notably, the patient had no respiratory complaints and maintained oxygen saturation of 98-99% on room air. Bronchoscopy revealed bronchoalveolar lavage (BAL) fluid with lymphocytic predominance, but cultures were negative and transbronchial biopsy was non-diagnostic and lymph node biopsies revealed normal lymphocytic tissue. Hematologic evaluation for plasma cell dyscrasia and amyloidosis was negative, though he was noted to have monoclonal gammopathy of undetermined significance. Additional workup revealed EBV positivity in BAL and serum (IgG+, IgM-), and weakly positive ANA and p-ANCA levels. Rheumatology consultation concluded that clinical features were not consistent with ANCA-associated vasculitis, additionally there was no evidence of diffuse alveolar hemorrhage on bronchoscopy. Empirical prednisone therapy led to a marked improvement in fatigue and interval resolution of the pulmonary opacities (Figure 1b). However, repeated steroid tapering attempts resulted in recurrent weakness, failure to thrive, and anemia, which normalized only during corticosteroid use. Given the relapsing course, bone marrow next-generation sequencing was pursued, identifying a pathogenic UBA1 mutation, confirming VEXAS syndrome. The patient has since been initiated on a JAK2 inhibitor and is tapering off steroids. Conclusion VEXAS syndrome is a late-onset, X-linked autoinflammatory disorder caused by somatic mutations in the UBA1 gene. It typically manifests with systemic inflammation, cytopenias, and multi-organ involvement, including pulmonary infiltrates, fevers, vasculitis, neutrophilic dermatoses, and bone marrow vacuolization of myeloid and erythroid precursors. The disease is often refractory to standard immunosuppressive therapy, with management focusing on corticosteroids and JAK inhibitors. This case underscores the importance of considering VEXAS syndrome in elderly men with unexplained systemic inflammation, autoimmune-like features and hematological abnormalities. This abstract is funded by: None

Abstract Rationale Interstitial lung disease (ILD) affects ∼50% of patients with systemic sclerosis (SSc) and is a leading cause of mortality. Visual assessment of ILD extent and morphologies, including ground-glass opacities (GGO) and reticular densities (RD), suffers from poor interobserver agreement, limiting prognostic consistency. CALIPER Quantitative CT (QCT) provides reproducible volumetric measures of parenchymal and vascular features. This study evaluated baseline QCT-derived lung features for association with transplant/mortality risk in SSc-ILD. Methods A retrospective cohort of SSc patients (≥18 years) seen at an academic center from 2007-2018 was identified using ICD codes, with ACR/EULAR 2013 SSc criteria confirmed by chart review. Inclusion required ILD on high-resolution CT (HRCT) ±2 years of SSc diagnosis, and PFTs ±6 months of HRCT. CALIPER quantified volumes of normal lung, GGO, RD, hyperlucency, honeycombing (HC), and pulmonary vascular-related structures (PVRS), which are expressed as percentages of total lung volume. Right heart catheterization confirmed pulmonary hypertension (PH) defined by 2022 ESC/ERS criteria (Eur Heart J, 2022). Cox hazards models assessed associations with combined mortality/transplant outcome, a priori adjusted for age, sex, diffuse SSc subtype, ILD duration, and PH (Column B), and further adjusted for baseline percent predicted FVC (ppFVC) and ppDLCO (Column C)(Table 1). Results Of 132 SSc-ILD patients, median SSc and ILD disease durations at HRCT were 1.4 (0.6, 2.4) and 0.0 (0.0, 0.5) years. Median feature percentages: total ILD 13.0% (IQR: 6.4, 21.0), GGO 10.2% (4.6, 16.9), RD 1.9% (0.8, 3.7), HC 0.03% (0.00, 0.09), PVRS 3.2% (2.3, 4.1). Median ppFVC was 81.1% (69.4, 92.6), and ppDLCO 60.0% (46.0, 75.7); 21 patients had PH. There were 2 transplants and 45 deaths. Every 5% increase in baseline total ILD and GGO associated with 22% (HR 1.22; 95% CI 1.12-1.33) and 24% (1.24; 1.12-1.36) higher risk of transplant/mortality on unadjusted models (Column A), respectively, remaining significant after a priori (CB) and full adjustment (CC)(Table 1). Every 1% increase in RD and PVRS conferred 19% (1.19; 1.08-1.31) and 33% (1.33; 1.08-1.63) higher risk of transplant/mortality in unadjusted models (CA); RD retained significance after a priori adjustment (1.17; 1.03-1.33), while PVRS trended non-significant in adjusted models. Conclusions In early SSc-ILD, QCT-derived GGO, RD, and PVRS provide robust prognostic value for mortality/transplant risk assessment, with small increases in baseline severity—at or below visual detection thresholds—associating with clinically meaningful risk increases. These findings support integrating baseline QCT biomarkers into risk stratification beyond clinical and PFT measures. This abstract is funded by: Rheumatology Research Foundation