Burger, C D

Abstract Rationale Pulmonary hypertension (PH) develops in up to 50% of patients with advanced interstitial lung disease (ILD) and is associated with increased morbidity, mortality, and impaired quality of life. Early recognition is essential, as available therapy for ILD-PH has been shown to improve outcomes. Identifying physiologic markers of PH may facilitate earlier referral for right heart catheterization (RHC) and initiation of targeted treatment. Thus, this study aimed to (1) compare functional parameters between ILD patients with and without RHC-confirmed PH, and (2) assess the applicability of previously proposed ILD-PH screening criteria. Methods We retrospectively analyzed ILD transplant candidates with available pre-transplant pulmonary function tests (FVC%, DLCO%), echocardiographic right-ventricular systolic pressure (RVSP), six-minute walk distance (6MWD) with oxygen requirement, and RHC data. PH was defined according to the 2022 ESC/ERS criteria. Functional parameters were compared between patients with and without PH. Among those without a prior PH diagnosis, screening thresholds derived from previously published tools were applied (RVSP ≥ 35 mmHg, DLCO < 40%, FVC/DLCO > 1.6, 6MWD < 350 m, or oxygen use during 6MWD). Results Of 107 ILD patients evaluated, 90 had complete RHC data (48 ILD-PH, 42 ILD without PH). Group comparisons are summarized in Table 1. Patients with PH had lower DLCO% (median 18.5 [11.5-26.7] vs 26.5 [20.0-34.7], p = 0.08), higher FVC/DLCO ratios (2.68 [2.1-3.4] vs 1.7 [1.4-2.6], p = 0.08), and higher RVSP (55 [39.7-63.2] vs 39.5 [29-48] mmHg, p = 0.002). Oxygen requirement during 6MWD was more frequent in ILD-PH (79.2% vs 61.9%, p = 0.08). Among patients with PH, 38 (79.16%) had no formal diagnosis prior to pre-transplant RHC. Of these cases, all (100%) met ≥3 screening criteria, most commonly DLCO < 40% (n = 38, 100%), FVC/DLCO > 1.6 (n = 37, 97.3%), and 6MWD < 350 m (n = 33, 86.8%). Additionally, 32 patients (84.21%) met ≥4 criteria and 8 (21.05%) met all five criteria. Conclusion In ILD transplant candidates, patients with PH had worse functional profiles when compared to those without PH, and nearly 80% of PH cases were previously undiagnosed. Systematic application of validated PH screening tools in ILD populations may facilitate earlier recognition, potentially improving patient outcomes. This abstract is funded by: None

Abstract Rationale Treatment of hematologic malignancies has been revolutionized by Chimeric antigen receptor T -cell (CAR-T) therapy. Pulmonary complications are increasingly being reported, however, there are no standardized timelines for pulmonary function test (PFTs) assessment before or after the infusion. We aimed to evaluate changes in lung function (TLC, RV, FEV1, and FEV1/FVC) pre- and post-CAR-T therapy and examine whether these parameters correlate with the development of specific pulmonary complications. Methods We conducted a retrospective chart review of patients above the age of 18 with any malignancy who received CAR-T therapy between June 12, 2018, and December 26, 2023. Pre-CAR-T PFTs were obtained closest to the infusion date, and post-CAR-T PFTs were recorded at the earliest available time following infusion. Pre- and post-CART pulmonary function tests were compared using non-parametric paired tests. In addition, we examined the relationship between baseline PFTs and the subsequent occurrence of pulmonary complications after CAR-T infusion. The Wilcoxon signed-rank test was applied to assess both the magnitude and direction of change while Sign test was used to evaluate only the direction to confirm the consistency of results. These tests were chosen due to small sample size and non-normal distribution of data. Results Among the 68 patients in our cohort, paired pre- and post- CAR-T measurements of pulmonary function were available for 18 patients. FEV1 declined significantly post-infusion (2.70 ± 0.81 L vs 2.28 ± 0.74 L; Z= -2.55, p = 0.011), the FEV1/FVC ratio remained stable (77.8 ± 8.0 vs 80.9 ± 12.2, p = 0.53). Mean TLC and RV remained stable (TLC 5.70 ± 1.18 L vs 4.66 ± 1.02 L, p = 0.17 and 2.13 ± 0.62 L vs 2.00 ± 0.70 L, p = 0.58). There was no significant correlation between the baseline lung function and the development of pulmonary complications. Conclusion Only the pattern of FEV1 decline following CAR-T therapy infusion demonstrates a significant decline, whereas other PFTs, although reduced, did not show significance. While these findings may suggest a restrictive ventilatory pattern, additional data on lung volumes are required to accurately characterize the underlying type of pulmonary function impairment. Although limited by small sample size and non-uniform timing of PFT assessments, this highlights the need for a routine pre-CAR-T pulmonary function evaluation to inform patient selection and baseline risk stratification. This abstract is funded by: None