Citations

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

Abstract Introduction Pulmonary artery masses have a broad differential. CT may offer initial characterization, but cardiac MRI and PET/CT provide more definitive information. Histopathologic evaluation is often required. We present a rare case of a pulmonary artery mass with an elevated IgG4 index, initially misclassified as more common benign and malignant entities. Case-Presentation: A 61-year-old never smoking female was referred to the pulmonary clinic for abnormal imaging. Her history was only for patent ductus arteriosus repair in infancy. She initially presented with pleuritic chest pain and was found to have near occlusive mass in the distal main pulmonary artery extending into the proximal left main pulmonary artery. This was presumed to be pulmonary embolism, and anticoagulation was started. At presentation, she reported mild dyspnea and improving chest pain, without constitutional symptoms. Cardiac MRI revealed restricted diffusion and enhancement consistent with pulmonary artery sarcoma. PET-CT revealed FDG avid pulmonary artery mass (SUV max 14.5) without other hypermetabolic lesions. She subsequently underwent resection of the main and proximal left PA mass resection with bovine pericardial reconstruction. Histopathology showed a dense lymphoplasmacytic infiltrate with prominent plasma cell infiltration, IgG4/IgG ratio of 40%, and > 10 IgG4 positive plasma cells per high power field. No histiocytic proliferation or evidence of other atypia. Her serum IgG4 level, CRP, ANCA serology, and fungal serology were normal. Discussion Here we present the case of isolated pulmonary artery mass with elevated IgG4 index of greater than 40% without other organ manifestations of IgG4 related disease (IgG4-RD). Cases of IgG4-RD related infiltration with a pulmonary artery mass have been reported, yet these typically present with other systemic manifestations, vascular inflammation, luminal stenosis, and/or pulmonary hypertension. Based on ACR 2019 IgG4 related disease classification criteria, these patients would not strictly meet criteria for IgG4 related disease. After extensive multidisciplinary discussion, we have elected to hold systemic treatment for IgG4-RD. She will be followed closely, monitoring new evidence of organ infiltration that would warrant systemic treatment. Conclusion Pulmonary artery masses should raise suspicion for various benign etiologies, such as chronic thromboembolism, and malignant entities, including pulmonary artery sarcoma. Cardiac MRI, PET/CT, and histopathology were critical in this patient’s evaluation. IgG4-related disease can rarely present as an intimal pulmonary artery mass. However, this is typically accompanied by systemic findings suggestive of IgG4-RD, other vascular infiltration, and/or pulmonary hypertension, all of which were absent in this patient. This abstract is funded by: None

Abstract Background Prostaglandin E2 (PGE2) exerts paradoxical effects in asthma, acting as both a protective mediator and a contributor to pathology depending on context. Its role is shaped by type 2 (T2)-status, eosinophilia, and exacerbation frequency. In epithelial cell cultures from asthmatic and healthy individuals, interleukin (IL)-13 suppresses PGE2 synthesis genes (PTGS2 and PGES) while upregulating HPGD, which encodes for the PGE2 catabolic enzyme 15-prostaglandin dehydrogenase (15-PGDH) (PMID:16751012), suggesting diminished PGE2 availability during T2 inflammation. Similarly, in aspirin-exacerbated respiratory disease (AERD), impaired cyclooxygenase disrupts PGE2 biosynthesis, fueling unchecked leukotriene production and eosinophilic inflammation (PMID: 30516547), underscoring PGE2’s protective role in limiting disease progression. Conversely, in nasal polyps, tuft cells are activated by IL-13 to produce PGE2 (PMID: 35608904), highlighting PGE2’s potential pathogenicity. Objective To assess associations between PGE2-pathway gene expression in bronchial brushings and asthma severity, and to determine how nasal polyp history modifies these relationships. Methods We analyzed bronchial epithelial brushings from 109 adults with asthma (mean age 42.4±12.1, 64% female, 52% severe asthma, 18% nasal polyps) using normalized and batch-corrected RNA-seq data from the baseline visit in the Severe Asthma Research Program (SARP)3 (PMID: 36796454). Age-adjusted and nasal polyp-adjusted relationships were calculated between ratios of PGE2 synthesis and metabolism genes and clinical outcomes (ASSESS score, FEV1 %predicted). The composite PGE2 score (PMID: 35608904), derived from nasal polyp analysis, was calculated from the average scaled log-normalized expression of six PGE2-responsive genes. All data were analyzed using a linear regression mixed model with a random effect for site. Results Ratios of PGE2 synthesis genes (PTGS1/2, PTGES2) to HPGD were significantly associated with greater disease severity (change in ASSESS Score) (Fig.1A, solid lines) and lower lung function (change in FEV1 %predicted) (Fig.1B, solid lines). These relationships persisted after adjusting for nasal polyps (Fig.1, dashed lines). The composite PGE2 score was also related to disease severity (Fig.1A, black solid line) but attenuated when nasal polyps were accounted for (Fig.1A, black dashed lines). Interestingly, lower lung function remained associated with the PGE2 score even after nasal polyp adjustment (Fig.1B, dashed black lines). Conclusions Our analysis demonstrates that the balance between PGE2 synthesis and degradation in the bronchial epithelium is closely linked to asthma severity and lung function, independent of nasal polyp status. Future work will integrate transcriptomic and clinical data longitudinally to establish whether PGE2 could serve as a biomarker for asthma trajectory. This abstract is funded by: HL115118 (LCD), U10HL109152 (S.E.W.), U10HL109172 (to E.I. and B.D.L), U10HL109168 (N.N.J.), U10HL109250 (S.C.E), U10HL109164 (W.C.M), U10HL109257 (M.C), and U10HL109146 (to P.G.W. and S.A.C.)

Abstract Rationale Type-1 inflammation in asthma leads to significant airway level changes independent of Type-2 inflammation and may underlie the severity seen in combined Type1/2 high disease. As IFNs can cause airway epithelial injury and impaired repair, we applied a novel interpretable machine learning algorithm, SLIDE, to analyze the transcriptome of airway epithelial brushings of mild-moderate (MMA) and severe asthma (SA) participants in the Immune Mechanisms in Severe Asthma (IMSA) cohort to identify latent/hidden factors of disease that associate with disease severity. Methods The expression of genes identified by SLIDE as part of a co-expression program was assessed in the full IMSA cohort by severity and in an independent cohort of the NHLBI Severe Asthma Research Program (SARP). We also examined associations of these genes with clinical asthma outcomes in both cohorts. Results SLIDE identified aberrant increased expression of membrane-tethered mucin genes, MUC1 and MUC4. MUC1 appeared in each of 5 significant latent factors associated with greater severity and MUC4 in 2/5. Standard DGE analysis also identified the gene CEACAM5 as a predictor of severity. Pathway analysis of latent factor genes revealed airway keratinization which may contribute to airway remodeling and worsening obstruction over time. Expression of MUC1, MUC4, and CEACAM5 were increased in SA compared to HC in both the full IMSA and separate SARP cohorts (p < 0.001 for all genes in both cohorts). Expression in MMA was consistently lower than in SA in both cohorts, reaching significance in IMSA (p < 0.01) but not consistently in SARP (MUC1 p = 0.04, MUC4 p = 0.27, CEACAM5 p = 0.27). Protein analysis of endobronchial biopsies by immunofluorescence staining showed a trend towards increased MUC1 protein content with evidence of secretion. MUC1, MUC4 and CEACAM5 were negatively correlated with FEV1 % predicted in both cohorts (IMSA: MUC1 r=-0.47, p < 0.01, MUC4 r=-0.47, p < 0.01, CEACAM5 r=-0.62, p < 0.01; SARP: MUC1 r=-0.19, p = 0.05, MUC4 r=-0.29, p < 0.01, CEACAM5 r=-0.51, p < 0.01). All three genes positively correlated with prospective exacerbations in both cohorts (IMSA: MUC1 r = 0.345, p = 0.01, MUC4 r = 0.216, p = 0.08, CEACAM5 r = 0.368, p < 0.01; SARP: MUC1 r = 0.22, p = 0.02, MUC4 r = 0.32, p < 0.01, CEACAM5 r = 0.38, p < 0.01). Conclusions The expression of MUC1, MUC4 and CEACAM5 increased with asthma severity in the airway epithelium and correlated with both prospective exacerbations and obstruction. As pathway analysis of genes in the significant latent factors were associated with airway keratinization aberrant expression of these mucins (with known signaling functions) may contribute to maladaptive repair and airway remodeling that drives obstruction over time, contributing to worse asthma outcomes. This abstract is funded by: NIH

Abstract Background Regulator of G protein signaling (RGS)2 terminates bronchoconstrictive Gaq signaling, and reductions in RGS2 expression associate with a hypercontractility phenotype. RGS2 promoter variants rs2746071 and rs2746072 are hypofunctional in gene reporter assays, and individuals with severe asthma homozygous for these two RGS2 variants experience higher asthma exacerbation rates. Whether these RGS2 promoter variants directly cause a hypercontractile human airway smooth muscle (HASM) phenotype is unknown. Methods We used the hTERT immortalized HASM cell line, derived from a human non-asthmatic donor. RGS2expression was reduced with siRNA (150nM anti-RGS2 vs. control siRNA) or through CRISPR transformation (Synthego©) to express the RGS2 promoter variants of interest, confirmed by Sanger sequencing. Gene and protein expression were quantified by qPCR and Western blotting. Intracellular Ca ++ flux and oscillation was measured with Fluo-8 (Abcam) with excitation/emission at 490/525 nm. HASM contractility to histamine treatment was measured using Traction Force Microscopy implemented in a 96-well plate format. Results Relative to cell lines with reference genotypes, HASM CRISPR transformed with the two RGS2 promoter variants exhibited a 41.8% (95% CI 28.6%--62.5%; p < 0.0001) reduction in RGS2 relative expression by qPCR, and a 35% (95% CI 8.6%—85.7%; p = 0.024) reduction in protein expression by Western blot. Methacholine-triggered calcium flux was nearly 50% greater for the cell lines with the RGS2 homozygous variants vs. those with reference genotypes (p = 0.043) as was the contractile response to histamine. HASM with reference genotypes exposed to anti-RGS2 siRNA showed the same phenotype, consistent with a causal relationship between the variants and expression (decreased) and receptor function (enhanced). Similarly, HASM CRISPR-transformed with the two RGS2 promoter variants exhibited an up to 3-fold increase in contraction magnitude (represented by strain energy, reported in pJ) in response to histamine >1uM (p < 0.05) relative to cell lines with reference genotypes. Conclusion Two promoter single nucleotide polymorphisms substitutions are sufficient to reduce RGS2 expression and induce a hypercontractile HASM phenotype. This abstract is funded by: AAAAI Bridge Award, NHLBI R21

Abstract Rationale The activity of fucosyltransferase 2 (FUT2) determines if mucin glycan structures in epithelial mucus include histo-blood group antigens (HBGAs). People with active FUT2 express HBGAs in epithelial mucus secretions and are terms “secretors”, while non-secretors lack HBGAs in their secretions because they have a FUT2 genotype that inactivates the glycosyl transferase. Prior research suggests that secretors who are blood type O (type O secretors) are susceptible to asthma exacerbations1 and that FUT2 knockout mice (functional non-secretors) are protected from mucus plugging in allergen challenge models2,3. We set out here to determine if secretor status influences mucus plug prevalence in asthma and to confirm if type O secretors are susceptible to asthma exacerbations. Methods We determined secretor status in asthma participants from the Severe Asthma Research Program-3 (SARP-3) cohort (N = 507) in two ways, a specific fucose lectin binding assay in sputum and FUT2 genotyping. Blood group type was determined using ABO genotyping. We analyzed mucus plug segment scores, asthma exacerbations rates and other clinical and biological features in patients stratified by secretor status and blood type (non-secretors, type O secretors, and non-type O secretors). Results Secretor status determined by lectin binding in sputum was strongly concordant with genotypic analysis. Within the SARP-3 cohort, 26.2% were non-secretors, 32.3% type were O secretors, and 41.4% were non-type O secretors. Mucus plug segment scores, annualized asthma exacerbation rates, and other measures of asthma severity were similar in non-secretors, type O secretors, and non-type O secretors (Table). Although type O secretors had increased values for fractional exhaled nitric oxide (FeNO) and higher expression of type 2 gene network genes in their sputum cells, measures of sputum eosinophil inflammation were not higher in this subgroup (Table). Conclusion Secretor status does not influence the prevalence of mucus plugging in asthma patients, and we did not confirm a prior report that type O secretors have an increased risk of asthma exacerbation. Although type O secretors have modestly increased FeNO levels and increased expression of type 2 immune genes in their sputum, it is not clear if this is a biologically important signal. 1. Innes et al. AJRCCM; 2011. 2. Saku et al. JACI; 2019. 3. Hara et al. AJRCMB; 2025 This abstract is funded by: The study was supported by the National Institutes of Health grants R01 HL080414 (JVF), P01 HL107202 (JVF), R01 HL164787 (JVF), U10 HL109172 (EI), U10 HL109152 (SEW), U10 HL109257 (MC), U10 HL109250 (SCE), U10 HL109146 (JVF), U10 HL109164 (ERB), U01 HL146002 (BDL), U10 HL109086 (DTM) and Sandler Asthma Basic Research Center at UCSF (JVF). The following companies provided financial support for study activities at the Coordinating and Clinical Centers beyond the third year of patient follow-up: AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Sanofi–Genzyme Regeneron, and Teva. These companies had no role in study design or data analysis, and the only restriction on the funds was that they be used to support the SARP initiative.