Karki, 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 Introduction VACTERL is an uncommon association of congenital anomalies that stands for vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities. In addition to these classical features, patients may present with airway abnormalities such as bronchial stenosis or bronchomalacia, which can lead to significant respiratory compromise. Severe bronchial stenosis is usually treated with open airway reconstruction or lung transplantation; however, this is associated with substantial risks, especially in patients with complicated congenital conditions. Interventional bronchoscopic techniques, such as paclitaxel-coated balloon dilatation, allow a less invasive alternative for restoring airway patency and reducing restenosis. We describe the case of a patient with VACTERL association and severe bronchial stenosis successfully treated with serial paclitaxel-coated balloon dilatations, avoiding the need for lung transplantation. Case description A 27-year-old male with VACTERL association presented with symptomatic left mainstem bronchial stenosis and complete right lung collapse. Bronchoscopic intervention was performed over lung transplantation because of the patient’s young age and high surgical risk. It revealed complete fibrotic obstruction of the right main bronchus and proximal stenosis of the left mainstem bronchus, measuring approximately 5-6 mm in diameter. Performing paclitaxel-coated balloon dilation showed progressive airway enlargement and clinical improvement. Under bronchoscopic guidance using a drug-coated balloon (diameter 8-10 mm, length 40 mm), which was placed in the narrowed segment and inflated for 2 minutes to expand the airway and deliver paclitaxel locally, thereby inhibiting cell proliferation and scar tissue formation. Subsequent follow-ups showed that the left mainstem bronchus diameter increased to 8-9 mm, with improvement in the airway patency and respiratory function, without any significant complications. Discussion Although the use of paclitaxel-coated balloon dilation for bronchial stenosis is still limited, this case illustrates its potential benefits as an adjunctive interventional therapy in patients with VACTERL association. The serial dilatations resulted in a progressive, sustained increase in airway diameter, from an initial 5-6 mm to approximately 8-9 mm at final follow-up in our patient (Figure 1). Compared with lung transplant, this intervention offers lower complication rates and the avoidance of chronic graft rejection and immunological complications, which are particularly relevant for young patients. This case report shows the potential of paclitaxel-coated balloon dilation as a safe, effective, and minimally invasive therapeutic option for managing bronchial stenosis in patients with complicated congenital disorders. This abstract is funded by: None

Abstract Introduction Pulsed Electric Field (PEF) Ablation has been used as an adjunct therapy for cancer. Robotic-Assisted Bronchoscopy (RAB) enables precise access to pulmonary lesions for biopsy and ablative therapy. However, anatomic obstructions within the airway may prohibit access to peripheral targets. We report a case in which robotic bronchoscopy navigation for the delivery of PEF was not initially possible due to a new anatomic airway obstruction secondary to radiation fibrosis. We were able to utilize therapeutic bronchoscopy to re-cannulate the airway and deliver the PEF via the robotic bronchoscope. Case Report A 68-year-old man with a history of left lung adenocarcinoma was treated with surgery, chemoradiation and durvalumab consolidation therapy. Surveillance imaging 4 years later revealed consolidation in the right upper mediastinum. A bronchoscopy brush biopsy confirmed adenocarcinoma and received systemic chemotherapy. Later a PET-CT showed a non FDG avid enlarged right paratracheal lesion. Follow-up CT revealed complete obstruction of the right middle lobar bronchus with associated middle lobe collapse likely secondary to radiation. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of the right paratracheal lesion confirmed malignancy on onsite cytopathology. Subsequently, we performed two PEF ablations targeting the involved lesion. Repeat PET-CT demonstrated two hypermetabolic foci in the right hilum and right supraclavicular region. However, the previously PEF treated paratracheal lesion was not PET avid. We used a RAB to navigate into the right upper lobe and identified the anterior segment to be obstructed in addition to the previously noted right middle lobe. Due to this, the robotic bronchoscope couldn’t be advanced to the right hilar PET avid lesion. Utilizing guidewires, balloon dilatation and fluoroscopy we re-cannulated the obstructed right upper lobe segment and subsequently advance the robotic bronchoscope to the target in the right upper lobe. Under cone-beam guidance, multiple biopsies were obtained and confirmed as malignant. Following this, the INUMI PEF needle was deployed. We delivered two PEF activations to the right hilar PET-avid lesion. Subsequent systemic staging using linear EBUS identified station 4R lymph node involvement, positive for malignancy on rapid onsite cytopathologic evaluation. The 4R lymph node was superior to the previously treated paratracheal lesion. We then deployed the INUMI PEF needle, and PEF ablation was performed successfully. Discussion To our knowledge, this is the first reported instance of combining robotic and therapeutic bronchoscopy to overcome airway obstruction to facilitate the distal treatment of peripheral target with PEF. This abstract is funded by: None

Abstract Introduction The diagnosis of fungal lung infections remains challenging as standard tests, such as bronchoalveolar lavage (BAL) antigen testing, often yield variable or inconclusive results. These limitations can delay appropriate therapy and may require additional tissue sampling for definitive diagnosis. Robotic-assisted bronchoscopy (RAB) biopsy has been primarily used as a minimally invasive technique for assessing suspicious peripheral pulmonary lesions (PPL). This case series highlights the diagnostic utility of RAB for identifying fungal infections within PPL when conventional BAL antigen analysis is non-diagnostic. Case Description Four patients with suspected infectious or malignant PPL underwent RAB-guided biopsy for diagnostic clarification, all yielding histopathologic confirmation of fungal disease. The first, a 73-year-old bilateral lung-transplant recipient with hemoptysis, had a negative BAL Aspergillus antigen despite RAB biopsy confirming Aspergillus infection. Similarly, a second 73-year-old man with chronic obstructive pulmonary disease (COPD) and esophageal adenocarcinoma had a negative BAL antigen, while RAB biopsy of bilateral cavitary lesions confirmed Aspergillus. Additionally, a 39-year-old woman with a nodule being evaluated for malignancy, had negative BAL Histoplasma antigen and PCR, whereas RAB biopsy confirmed Histoplasma capsulatum. In contrast, a 56-year-old woman with a right-lower-lobe nodule had a positive BAL Aspergillus antigen that aligned with the histopathologic biopsy findings. Discussion BAL-based antigen testing demonstrates variable diagnostic accuracy in fungal lung disease. Reported sensitivities for Aspergillus detection are typically high in meta-analysis, approximately 80%-90%, but clinical performance in the immunocompromised or high-risk patients is often substantially lower. Similarly, while BAL antigen testing for Histoplasma performs well in disseminated infections, it often fails to detect localized pulmonary disease. In this series, three out of four patients had negative BAL results in the presence of histopathologic confirmation of fungal infection. While current guidelines consider BAL positivity supportive of a “probable” diagnosis, tissue histopathology remains the gold standard for a “proven” infection. These findings emphasize the value and capability of RAB in obtaining direct tissue confirmation when conventional testing, such as BAL antigen analysis, is non-diagnostic. Conclusion RAB-guided biopsy of PPLs offers the opportunity for histopathologic confirmation of fungal infection when BAL testing is non-diagnostic. This approach can enhance upfront diagnostic yield in patients with suspected fungal pulmonary infections, avoiding delays in diagnosis and treatment initiation. 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

Abstract Background With recent advances in oncology, tyrosine kinase inhibitors like imatinib play a significant role in gastrointestinal stromal tumor (GIST) treatment but can cause rare pulmonary complications. When new respiratory symptoms arise after starting these agents, differentiating drug toxicity from other lung diseases is important for timely management. Case Presentation A 72-year-old man with GIST, recently started on imatinib, presented with acute dyspnea and hypoxia. His medical history included chronic obstructive pulmonary disease and a 40-pack-year smoking history. Chest CT revealed new bilateral interstitial infiltrates absent on imaging two months ago, prior to imatinib initiation. The differential diagnosis included imatinib-induced pneumonitis versus atypical infection. Bronchoscopy showed yellowish nodular mucosa throughout the trachea and bronchi, mucus plugging, and airway narrowing in the left lower lobe. Endobronchial biopsies demonstrated amyloid deposits consistent with tracheobronchial amyloidosis. The bronchoalveolar lavage was negative for infection and, therefore, corticosteroid therapy was initiated, resulting in clinical and radiographic improvement. The findings supported a diagnosis of imatinib-induced pneumonitis coexisting with tracheobronchial amyloidosis. Discussion This case highlights the diagnostic challenges when drug-induced pneumonitis occurs along with structural airway abnormalities. Tracheobronchial amyloidosis, although rare, can cause airway obstruction and coexist with inflammatory lung conditions. The temporal association with imatinib, exclusion of infection, and steroid responsiveness indicate imatinib-induced pneumonitis as the primary cause of the acute symptoms, with concurrent amyloid deposition contributing to airway pathology. Conclusion In patients developing new pulmonary symptoms after starting tyrosine kinase inhibitors, drug-induced pneumonitis should be strongly suspected. The coexistence of airway diseases such as tracheobronchial amyloidosis can complicate diagnosis and management, highlighting the need for thorough evaluation including bronchoscopy and tissue biopsy to guide treatment. This abstract is funded by: None

Abstract RATIONALE There are limited studies evaluating the association between chimeric antigen receptor T-cell (CAR-T) therapy and interstitial lung abnormalities (ILA). Our study aims to investigate this potential relationship to better understand pulmonary complications following CAR-T therapy. Methods We conducted a retrospective chart review of patients aged 18 or older with any malignancy who received CAR-T therapy between June 12, 2018, and December 26, 2023. Chest imaging, including PET or CT scans, was reviewed for each patient; the closest scan before CAR-T therapy and the most recent scan afterward. We identified ILA based on findings that included ground-glass opacities, reticular abnormalities, traction bronchiectasis, honeycombing, or non-emphysematous cysts involving more than 5% of lung zones. We excluded dependent atelectasis, paraspinal fibrosis, aspiration-related changes, mild focal or unilateral abnormalities, and smoking-related centrilobular nodularity without other findings. Results A total of 66 patients had adequate imaging data both before and after CAR-T infusion. Before therapy, 17 patients (25.8%) demonstrated ILA, while 49 (74.2%) did not. Following CAR-T therapy, the overall prevalence of ILA increased to 31 patients (47.0%). Among those who did not have ILA before CAR-T, 16 of 49 (32.7%) developed new ILA following therapy. Conversely, among those with pre-existing ILA, 14 of 17 (82.4%) showed persistent or progressive ILA post-CAR-T. This distribution demonstrated a statistically significant association between pre- and post-CAR-T ILA status (χ² = 10.8, p = 0.001), indicating that pre-CAR-T ILA status strongly predicted post-CAR-T ILA persistence or worsening. When evaluating post-CAR-T ILA in relation to clinical outcomes, among those with pre-CAR-T ILA, 52.9% (n = 9) were deceased at follow-up, compared to 55.1% (n = 27) among patients without ILA. The difference in mortality between the groups was not statistically significant (χ² = 2.34, p = 0.31). 19 of 31 patients (61.3%) with post-CAR-T ILA were deceased at last follow-up, compared with 17 of 37 (45.9%) in those without ILA. Although mortality was numerically higher among patients with post-CAR-T ILA, this difference did not reach statistical significance (χ² = 1.04, p = 0.308). Conclusion Our study demonstrates a statistically significant association between pre- and post-CAR-T interstitial lung abnormalities, suggesting that CAR-T therapy may contribute to the progression or development of ILAs. These findings highlight the need for closer pulmonary monitoring during CAR-T treatment. This abstract is funded by: None