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Abstract Rationale Seralutinib is an investigational, first-in-class tyrosine kinase inhibitor designed for inhalation and selective for PDGFRα, PDGFRβ, CSF1R, and cKIT, targeting proliferation, inflammation, and fibrosis ─ three core drivers of pulmonary vascular remodeling in PAH. The phase 2 TORREY trial of seralutinib added to standard-of-care treatment in adults with PAH WHO FC II or III met its primary endpoint of a statistically significant reduction in pulmonary vascular resistance (PVR) vs. placebo at 24 weeks. Methods PROSERA (NCT05934526), a phase 3, randomized, double-blind, placebo-controlled, multicenter trial, evaluated the efficacy and safety of inhaled seralutinib in PAH patients treated for up to 48 weeks. Eligible patients (WHO Group 1 PH, FC II or III; REVEAL Lite 2 Risk Score ≥5 or NT-proBNP ≥300 ng/L or PVR ≥800 dyne•s/cm5) on standard background therapy were randomized 1:1 to seralutinib 90 mg or placebo delivered by dry powder inhaler twice daily. The primary endpoint was change in six-minute walk distance (6MWD) from baseline to week 24 in the seralutinib treatment group vs. placebo. Key secondary endpoints included: time to clinical worsening (TTCW), proportion of patients with clinical improvement at week 24, change in NT-proBNP from baseline to week 24, and proportion of patients with ≥1-point decrease from baseline in REVEAL Lite 2 Risk Score at week 24. Safety endpoints included incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs (SAEs). Patients who completed blinded treatment could be eligible to participate in an open-label extension study. Preliminary Blinded Results 390 patients were randomized at 132 sites worldwide. At baseline, mean age was 50.0 years. PAH etiologies included 61.0% idiopathic, 9.7% heritable, and 22.3% associated with connective tissue disease. 25.6% of patients were WHO FC II and 74.4% FC III. Mean time from diagnosis was TBD years. Most patients were receiving 2 (39.2%) or ≥ 3 (54.6%) PAH medications, 29.2% were receiving parenteral prostacyclin. Baseline PVR was 798.4 dyne•s/cm5, 6MWD was 373.7 m, and NT-proBNP was 986.8 ng/L. The difference in 6MWD from baseline to week 24 between seralutinib and placebo was TBD [SD] m (p=TBD). Secondary endpoints of TTCW, clinical improvement, NT-proBNP, and REVEAL Lite 2 Risk Score will be reported. The most common AEs were TBD (x%) and TBD (y%). SAEs and discontinuations related to AE will be reported. Conclusions The PROSERA study demonstrates⋯ [to be updated following unblinding of the data]. Funding Gossamer Bio, Inc. This abstract is funded by: Gossamer Bio, Inc.

Abstract Introduction Insulin resistance is prevalent in pulmonary arterial hypertension (PAH) and is associated with worse health outcomes. The triglyceride-glucose (TyG) index as a measure of insulin resistance is superior to HOMA-IR in predicting metabolic syndrome. This study utilizes the Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics (PVDOMICS) data registry to further examine the relationship between TyG index and reported quality of life (QOL) in patients with PAH. Methods 327 patients with a diagnosis of PAH in PVDOMICS were stratified into insulin resistant (IR) (TyG index >8.55) and insulin sensitive (IS) (TyG < 8.55) groups where TyG = (ln[triglyceride*glucose/2]. QOL measures assessed were the Minnesota Living With Heart Failure (MLHF) Physical and Emotional domain surveys, Short Form (36) (SF-36) Physical and Mental Component Health Surveys (PCS and MCS, respectively), and emPHasis-10 (E10). Reported measures between groups were compared using least squares means adjusted for age, sex, fat mass index (FMI), PAH etiology, 6-minute walk distance (6MWD) and NT-pro-brain natriuretic peptide (NTproBNP). Kaplan-Meier curves and Cox proportional hazards models adjusted for these same variables were performed to assess difference in survival between groups. Results 155 patients with PAH (47%) were classified as IR. Patients with IR were more likely to be female (79% vs 69%, p = 0.04), more likely to be non-Hispanic white, and less likely to be non-Hispanic Black (p = 0.045). There were no differences in age or etiology of PAH between groups. Patients with IR had higher body mass index (30.9 vs 27.3 kg/m2, p < 0.001) with higher FMI (16.2 vs 13.2 kg/m2, p < 0.001). Patients with IR were more likely to have diabetes mellitus (24% vs 11%, p = 0.004). Compared to their IS counterparts and after adjusting for possible confounders, patients with IR had higher (worse QOL) MLHF physical domain (p = 0.04), higher (worse QOL) emPhasis-10 scores (p = 0.03), and lower (worse QOL) SF36 physical component scores (p = 0.03) (Figure). IR and IS groups had no significant differences in the MLHF emotional domain and SF36 mental component scores. After multivariable adjustment, there was no difference in survival between groups (HR 0.91, 95% CI 0.56-1.46). Conclusion Patients with PAH and IR had worse QOL compared to their IS counterparts but no difference in survival in this large prospective cohort. This abstract is funded by: This work was supported by the National Institutes of Health grants K23HL 141584, R01 HL173533

Abstract Rationale This Registry was designed to prospectively evaluate the efficacy of extracorporeal photopheresis (ECP) to arrest the rate of FEV1 decline (FEV1 decline) and prolong survival in lung allograft recipients with Bronchiolitis Obliterans refractory to standard of care therapy. Methods After IRB approval, 258 lung transplant recipients were enrolled from 20 US lung transplant centers. Subjects were assigned to ECP treatment (ECPRx) (i.e., 24 procedures over 6 months) at or a few months after enrollment based on spirometric criteria. Maintenance ECPRx (mECP) was at the discretion of managing clinicians. Rate of FEV1 decline in mL/month (FEV1 decline) was compared between 6 months prior to and 6 & 12 months after ECPRx initiation using linear mixed effects models. Time 0 for survival was set as the start of ECPRx for generation of Kaplan-Meier curves. Hazard Ratios (HR) with 95% confidence intervals (lower-upper) were generated using Cox Proportional Hazards Regression to characterize significant (p < 0.05) independent associations of mECP and/or any other covariates (i.e., demographic, operative, enrollment site, spirometric ) and survival. Results An 89% (78%-96%) decrease in the FEV1 decline was observed 12 months after ECPRx initiation in 191 participants assigned to ECPRx. FEV1 decline (-164 mL/month: 144-185) was greater (p < 0.001) in participants who expired within six months of Time 0 (n = 28) vs participants (-111 mL/month: 101-120) who died six months after Time 0 (n = 77). Of 159 participants who survived for at least six months after ECPRx initiation, 40 participants without mECP, who had up to 24 ECPRx (ECPRx: n = 19), had a lower survival HR: 2.43(1.75-3.4) (p < 0.001) relative to 119 participants who received mECP (ECPRx: n = 86)(see Figure). The response to ECPRx (% Change in FEV1 decline prior to and 6 months after 1st ECP) was similar between subcohorts (No mECP: -81 decrease vs mECP: -85%, p = 0.3). The association of mECP persisted after multivariate adjustment HR 1.8 (1.8-2.7)(p = 0.002) using significant covariates: FEV1 HR 0.37 (0.3-0.5), FEV1 decline HR 0.001 (0.001-0.04), Male Gender HR 2.4 (1.7-3.4); Reflux Disease HR 1.8 (1.2-2.8); Coronary Disease HR 1.8 (1.2-2.7). Conclusions This analysis indicates that mECP is independently associated with enhanced survival most likely due to attenuation of relapse six months after ECP initiation based on similar initial response to ECPRx. A risk-adjusted, control cohort is being pursued to facilitate submission of a scientifically rigorous petition to CMS to expand the ECP National Coverage Decision to include BOS predicated on CMS 2024 scientific guidelines. This abstract is funded by: Therakos Inc

Abstract Rationale High rates of poor asthma control have resulted in over 8 million annual exacerbations. With the introduction of biologic agents, even patients with severe persistent asthma are often able to avoid emergency department (ED) use and hospitalization with appropriate preventive treatment. However, access to and utilization of guideline-recommended biologic agents has remained suboptimal. This interview-based study was designed to evaluate barriers hindering access to preventive treatments from the patient perspective. Methods Using electronic health records of a large state-wide healthcare system serving a diverse population, we identified adults with asthma who experienced at least one hospital admission or ED visit in 2025 for acute asthma exacerbation while being treated with a medium or high dose inhaled corticosteroid and at least one other controller therapy. Eligible individuals were contacted to offer participation in a semi-structured interview focused on patient perceived care access barriers. We aimed for 20-25 participants, guided by thematic saturation. All interviews were transcribed and analyzed using NVivo software. Results Twenty-one participants were interviewed, reporting barriers to asthma care across five thematic areas: cost, care availability, logistical barriers, medical literacy and preferences, and desire for rapidly effective treatment (Table 1). Participants reported high out of pocket costs resulting in skipping refills or routine clinical visits, with some participants reporting seeking care in ED or hospital settings due to unaffordable costs encountered through traditional outpatient care routes. Participants also reported not bringing symptoms to outpatient care providers’ attention due to their chronicity and the perception that these symptoms were “normal” over time.When discussing outpatient specialist access, participants highlighted barriers including long wait times, travel distance, referral restrictions, and clinic hours resulting in conflicts limiting scheduling opportunities. Many participants also reported feeling more comfortable with seeking care through inpatient or emergency care facilitates due to perceived faster response time of providers and more immediate effectiveness of treatments provided. Finally, participants reported limited understanding of treatment goals, anticipated disease and treatment course, and side effects associated with rescue treatments such as systemic steroids. Conclusions This qualitative study provides rich data on barriers to care experienced by patients with poorly controlled asthma. Our results highlight novel potential areas for intervention including target areas to clarify communication of symptom control goals and treatment expectations. Future research should explore the most effective ways to address these care barriers with the goal of improving access to preventative therapies among patients living with asthma. This abstract is funded by: University of Maryland Baltimore, Institute for Clinical & Translational Research (ICTR) [grant number UM1TR004926-02]

Abstract Background Takayasu arteritis (TA) is a rare large-vessel vasculitis that can involve pulmonary arteries, potentially leading to pulmonary hypertension (PH). Noninvasive evaluation by echocardiography is often used, but its reliability in confirming and characterizing PH in TA is unclear. We investigated the role of invasive hemodynamic testing in TA patients with suspected PH. Methods We retrospectively identified 10 patients with TA meeting 2022 ACR criteria and suspected PH based on symptoms and/or echocardiography; all underwent echocardiography followed by right heart catheterization (RHC).PH was defined as mean pulmonary artery pressure (mPAP) >20 mmHg. PH was classified as pre-capillary (pulmonary artery wedge pressure [PAWP] ≤15 mmHg), post-capillary (PAWP >15 mmHg), or combined (PAWP >15 mmHg with elevated pulmonary vascular resistance). Echocardiographic parameters were collected where available, along with invasive hemodynamics, cardiac biomarkers (BNP/NT-proBNP), inflammatory markers (ESR, CRP), NYHA functional class, and outcomes. Results Median age was 44 years (range 18-58), and 90% were female. Based on invasive hemodynamics, pre-capillary PH was present in 5 patients, combined pre-/post-capillary PH in 3, and isolated post-capillary PH in 2. Median mPAP was 38 mmHg (IQR 30-55), median pulmonary vascular resistance 3.5 Wood units (IQR 2.3-8.7), and median PAWP 15 mmHg (IQR 8-24). Echocardiography frequently underestimated disease severity. Several patients with absent or low tricuspid regurgitation velocity (≤1.0 m/s), where measurable, demonstrated severe pre-capillary PH on RHC, including pulmonary vascular resistance >6 Wood units. Among patients with available data, NT-proBNP levels ranged from 59 to 51,968 pg/mL, and inflammatory markers varied widely (CRP <0.3 to 107.9 mg/L). Among patients with available NYHA data, most were class II-III. Conclusions In this TA cohort, RHC was essential to confirm and phenotype PH, which was present in the majority of those with suspected PH. Echocardiography alone often underestimated or misclassified PH in TA - in one case missing severe pre-capillary PH due to an absent TR signal, and in another failing to discern elevated left-heart filling pressure. Invasive assessment prevented missed diagnoses and misclassification, ensuring appropriate management of TA-associated PH This abstract is funded by: None

Abstract Purpose Bronchiectasis is a condition characterized by chronic cough, recurrent infections, and progressive airway damage that is rising in prevalence. While often idiopathic, a subset of patients have a genetic cause such as cystic fibrosis (CF), primary ciliary dyskinesia (PCD), or alpha-1-antitrypsin deficiency (A1ATD). Genetic causes for bronchiectasis should be considered in patients with diffuse bronchiectasis involving ≥2 lobes, especially in those with early onset of symptoms, recurrent otitis media or chronic rhinosinusitis, infertility, organ laterality defects (e.g., situs inversus), exocrine pancreatic insufficiency or family history of bronchiectasis. Genetic testing may impact management decisions. Methods The Mayo Clinic Center for Individualized Medicine developed the Program for Rare and Undiagnosed Diseases (PRaUD) Genetic Testing and Counseling Unit (GTAC) provides abbreviated, point-of-care genetic counseling, and DNA sequencing-based testing. Patients with bronchiectasis evaluated by GTAC underwent exome or genome-based 52-gene panels which included PCD, CF, and A1ATD (SERPINA1)-associated genes. Sequencing panes results were reviewed and interpreted by a multidisciplinary team including genetic counselors, geneticists, and pulmonologists. Results From July 2022 to December 2025, 203 patients were identified; 163 patients completed testing (74% female, 93% white). A molecular diagnosis was confirmed in 10.4% (17/163) of cases, with known pathogenic variants identified in RSPH4A, SERPINA1 (A1ATD), and CFTR (CF). Variants of uncertain significance (VUS) were identified in 24% of patients. Notably, 11.6% (19/163) were identified as CF carriers, a rate significantly higher than the general European-ancestry population (∼4%). Clinical management was impacted for two patients, including the initiation of targeted CFTR modulator therapy in one patient with CF-related disorder (CFTRD) and one CFTR pathogenic variant heterozygote. Conclusions Genetic counselor-supported DNA sequencing for bronchiectasis led to an increased identification of genes that cause bronchiectasis. Interestingly, we found a high rate of CFTR heterozygote variant carriers in our clinic cohort, this aligns with the findings of other studies that CFTR variant carriers can have an increased frequency of bronchiectasis. The identification of pathogenic variants and VUS helps facilitate a diagnosis or potential genetic cause in a significant proportion of patients and highlights the need for further research in understanding the epidemiology of CF, PCD, and A1ATD-related variant genotypes in patients with bronchiectasis. Clinical Implications Comprehensive DNA sequencing, combined with genetic counseling and support from genetic counselors in partnership with pulmonologists can advance precision diagnostics and care for patients with bronchiectasis. This abstract is funded by: None

Abstract Rationale Blood eosinophil count (BEC) has emerged as a marker of inflammatory endotypes in bronchiectasis. We examined whether bacterial and mold respiratory culture profiles differ by BEC, comparing patients with BEC ≥300 cells/μL to those with lower BEC. Methods We analyzed patients with bronchiectasis evaluated at a specialized clinic (2019-2025) who had contemporaneous respiratory bacterial and fungal cultures and BEC. Patients were stratified by BEC <300 vs ≥ 300 cells/μL; those with BEC <300 were further subclassified (<100 and 100-299 cells/μL) for figure presentation only. Cultures were evaluated for overall growth and organism-specific prevalence across eosinophil strata, focusing on the most frequently isolated organisms. Group comparisons were performed using Fisher’s exact test. Results A total of 608 patients met inclusion criteria (median age 69 years [IQR 61-77], 72% female); 138 (22.7%) had BEC ≥300 cells/μL. Bacterial growth occurred in 277 patients (45.6%) and mold growth in 366 (60.2%). The odds of bacterial growth were similar between BEC ≥300 and <300 groups (47.1% vs 45.2%). In contrast, BEC ≥300 was associated with higher odds of mold growth (68.1% vs 58.0%; OR 1.54, p = 0.038). Pseudomonas species (18.9%) were the most common bacterial isolates and comprised a greater proportion of all bacterial isolates in patients with BEC ≥300 compared with lower BEC (44.7% vs 30.0%; OR 1.89, p = 0.019). Penicillium species (27.5%), followed by Aspergillus (26.9%), were the most frequently isolated molds, with no differences in distribution across BEC strata. Conclusions BEC ≥300 cells/μL was associated with increased odds of respiratory mold growth and enrichment of Pseudomonas species, suggesting that eosinophil-defined endotypes may identify patients with distinct airway microbiologic patterns that could inform future phenotyping and treatment strategies. This abstract is funded by: None

Abstract Background Anxiety and depression have been reported in patients with fibrotic interstitial lung disease (f-ILD) and may be detected or evaluated with use of patient reported outcome measures (PROMs). The Generalized Anxiety Disorder-7 (GAD-7) is a screening tool for general anxiety, and the Patient Health Questionnaire (PHQ-9) is a screening tool for depression. We hypothesize that anxiety and depression in f-ILD may be independently associated with increased self-reported dyspnea and decreased physical activity. Methods This was a prospective observational cohort study conducted at a tertiary care institution. Patients with f-ILD were electronically sent PROMs to be completed at study enrollment, three months and six months. Patients also wore an activity monitor (ActiGraph) for 7 days at each time point. Included PROMs were the Modified Medical Research Council dyspnea scale (mMRC), GAD-7, and PHQ-9. The primary outcome was physical activity defined by average steps per day at each timepoint. Two sided, two sample t- tests were used to compare mean mMRC scores between participants with and without anxiety and depression. Mixed effects linear regression models with each patient as a random effect were used to evaluate the association between PROMS and physical activity. Models were adjusted for age, sex, FVC, and timepoint. Results Forty-eight patients were enrolled (mean age 69, female 46%, mean forced vital capacity (FVC%) 80%) and 45 completed baseline PROM and activity measures. In our cohort, 22 (46%) had background clinical anxiety and 17 (31%) had depression. In those with anxiety, 59% were classified as moderate and 2% as severe, while 47% were classified as moderate and 1% as severe in those with depression. Higher mMRC dyspnea scores were associated with both anxiety (1.955, p = 0.058) and depression (2.118, p = 0.022). Results from regression models indicated a one-point increase in GAD7, PHQ-9, and mMRC was associated with decrease in physical activity as defined by steps per day) ([GAD: -272 steps, p = 0.022], [PHQ-9: -188 steps, p = 0.014], [mMRC: -741 steps, p = 0.007]). Conclusions Patients with f-ILD and clinical anxiety and depression reported greater dyspnea and decreased measured physical activity. This abstract is funded by: None

Abstract Rationale Impaired lung health may serve as a risk factor for, and a post-acute sequela of, SARS-CoV-2 infection. Yet most prior studies of lung health sequelae of COVID-19 lacked information on pre-infection lung health, a major antecedent confounder. To identify associations of COVID-19 with changes in lung health, we leveraged paired pre- and post-pandemic data on respiratory symptoms, lung function, and lung structure in a general population-based cohort. Methods We studied participants in the Multi-Ethnic Study of Atherosclerosis Lung Study with paired pre-pandemic (2016-2018) and post-pandemic (2022-2024) assessments of respiratory symptoms, spirometry, and lung CT. SARS-CoV-2 infection (2020-2023) was ascertained using a composite of questionnaires, serology, and medical record adjudication, and classified as severe (requiring hospitalization) or non-severe (not requiring hospitalization). Lung health was assessed by questionnaire (mMRC grade ≥2 dyspnea, chronic cough, chronic phlegm, chronic bronchitis), pre-bronchodilator spirometry (FEV1, FVC, FEV1:FVC), and lung density on non-contrast lung CT (% low attenuation areas, % high attenuation areas). Each post-pandemic lung health measure was regressed on infection history and the corresponding pre-pandemic lung health measure, adjusting for age at post-pandemic exam, sex, race/ethnicity, smoking status, and vaccination status at infection. Sensitivity analyses were included- (a) restriction to participants without pre-pandemic respiratory symptoms and (b) with additional adjustment for time since infection and variant wave. Results Among 2,015 participants (mean age 77.2±7.5 years; 55% female; 40% non-Hispanic White; 25% Black; 11% Asian; 23% Hispanic/Latino), 59 (3%) experienced severe and 506 (25%) non-severe SARS-CoV-2 infection. The prevalence of respiratory symptoms was similar or slightly higher at the post- vs. pre-pandemic exam (grade ≥2 dyspnea: 14% vs. 10%; chronic cough: 10% vs. 8%; chronic phlegm: 9% vs. 8%; chronic bronchitis: 4% vs. 4%; p-values <0.0001). Compared with participants without infection, those with severe infection had higher odds of chronic cough (OR:2.9, 95%CI:1.3-6.3) and chronic bronchitis (OR:3.3, 95%CI:1.2-9.0) at the post-pandemic exam (Table). Associations were stronger among individuals infected >90 days prior to the post-pandemic assessment and during pre-Omicron waves. Results were similar when restricted to participants without pre-pandemic symptoms. No significant associations were observed for non-severe infection (vs. no infection) or for any other lung health outcomes. Conclusions Controlling for pre-pandemic lung health, severe COVID-19 was associated with increased odds of chronic cough and chronic bronchitis but not with changes in lung function or structure in a general population-based sample. Non-severe COVID-19 was not associated with lung health outcomes. This abstract is funded by: OT2HL156812, R21HL165405, R01HL077612, 75N92025D00022, 75N92025D00026, 75N92020D00002, 75N92025D00024, 75N92025D00027, 75N92025D00025, 75N92025D00028

Abstract Rationale Fungal infections are a significant cause of morbidity in lung transplant recipients. Infections caused by non-Aspergillus species (spp.) fungi, such as Alternaria, Cladosporium, Fusarium, Lomentospora, Mucorales, and Scedosporium, among others, occur infrequently, but recognized cases are increasing. There is a paucity of data assessing post-transplant outcomes following pre-transplant fungal colonization with these non-Aspergillus spp. fungal organisms. Methods We retrospectively reviewed all adult (>18 years) patients who underwent bilateral lung transplantation at either Mayo Clinic Rochester and Mayo Clinic Jacksonville between 01/01/2016 through 12/31/2024, comparing those with pre-transplant fungal colonization to those without fungal colonization. Fungal colonization was defined as positive respiratory culture in either sputum, tracheal aspirate, bronchial brush, bronchoalveolar lavage (BAL) fluid, or swab of explanted lung in asymptomatic patients without radiological or endobronchial evidence of infection. Patients who underwent single lung transplantation, multi-organ transplantation, and those who had previously undergone organ transplantation were excluded from the study. Our primary outcome was severe post-transplant fungal infection, which we defined as proven or probable invasive fungal infection (based on EORTC/MSG criteria), that required hospitalization or additional procedural intervention. Baseline characteristics were summarized using medians with interquartile ranges or counts with percentages, group balance was assessed using standardized mean differences, and associations with post-transplant fungal infection and mortality were evaluated using unadjusted risk ratios (RR) with 95% confidence intervals. Results Of the 449 lung transplant recipients who were included in analysis, a total of 83 patients (18.5%) had pre-transplant fungal colonization, 45 patients (10.0%) with Aspergillus spp. and 38 patients (8.5%) with non-Aspergillus fungi. Compared to those without pre-transplant fungal colonization (n = 366), those with fungal colonization differed significantly in age, gender, body mass index (BMI), Cytomegalovirus (CMV) mismatch status, and transplant indication. The pre-transplant fungal colonization cohort had 4 patients (4.8%) develop any severe fungal infection post-transplant (2 Aspergillus spp. and 2 non-Aspergillus spp.). Pre-transplant fungal colonization was not associated with severe post-transplant fungal infection [RR 1.36 (0.45-4.06)] or with severe post-transplant Aspergillus spp. infection specifically [RR 0.80 (0.18-3.55)]. Unadjusted mortality was also not statistically significant [RR 0.74 (0.47-1.17)]. Conclusions In our cohort of bilateral lung transplant recipients, pre-transplant fungal colonization was not associated with severe post-transplant invasive fungal infection. Although limited by the retrospective nature of the study, the results provide supportive evidence that pre-transplant fungal colonization should not be a precluding factor for undergoing lung transplantation. This abstract is funded by: None