Citations

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

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

Abstract Introduction Medullary thyroid cancer (MTC) is an uncommon malignancy arising from the C-cells of the thyroid gland. It makes up 2% of all thyroid cancers, with both familial and sporadic patterns noted. It is most commonly diagnosed in the fourth to sixth decade of life, with the lungs being a common site of metastasis. We present a case of metastatic MTC with a rare pulmonary presentation. Case Description The patient presented at the age of 28 after having a chronic complaint of stomach pain and diarrhea. Imaging of the abdomen revealed small nodules in the lower pulmonary fields. Dedicated imaging of the chest was subsequently ordered. This study was notable for an enlarged left lobe of the thyroid extending into the mediastinum with two large mediastinal lymph nodes. A fine-needle aspiration of the left neck lymph node was consistent with MTC and there were hematologic findings of elevated calcitonin and CEA. Testing for the RET proto-oncogene was negative. Pathology on total thyroidectomy confirmed the diagnosis, with further sampling identifying metastasis in the thoracic spine (T12). Initial therapy with pazopanib was commenced. After some time on stable therapy, the patient was noted to have waxing and waning pulmonary micro-nodularity associated with increase in his calcitonin levels. There was a finding of a miliary pattern of disease on chest imaging. The pulmonary service was consulted due to these findings in conjunction with sub-acute cough. Pulmonary biopsy was performed, with findings of nodular amyloidosis; Congo red stain highlighted amyloid deposition. Immunohistochemical studies were performed, revealing rare cell groups that were positive for calcitonin, CEA, CAM5.2, TTF-1, chromogranin, and synaptophysin. After further discussion with the Pathology service, the patient was given formal diagnosis of amyloid deposition of the Acal subtype due to metastatic medullary thyroid cancer. Discussion This case highlights a patient diagnosed with sporadic MTC, later found to have metastatic related pulmonary amyloid deposition. While local amyloid deposition can be seen in MTC, it is unusual to have diffuse parenchymal disease due todiffuse parenchymal disease due to distant deposition. There are only four other instances in the literature of a similar presentation. Amyloid deposition is associated with worse outcomes, but the patient had a good outcome with treatment by a tyrosine-kinase inhibitor.

Abstract Rationale: Lymphoid Interstitial Pneumonia (LIP) is a rare interstitial lung disease characterized as a benign lymphoproliferative pulmonary condition. It is often associated with autoimmune conditions such as Sjögren's syndrome, immune dysregulatory syndromes, and common variable immunodeficiency. The incidence and prevalence of LIP remain unclear. While fluorodeoxyglucose (FDG) Positron Emission Tomography (PET/CT) findings have been documented for various diffuse parenchymal lung diseases, data specific to LIP is limited. This study aims to assess the utility of PET/CT in the evaluation of malignancy in patients with LIP, in addition to describing PET/CT findings in patients with known LIP who underwent PET/CT for any reason. Methods: This retrospective study involved a reviewof electronic medical records within the Mayo Clinic Enterprise to identify patients with an established diagnosis of LIP who had undergone PET/CT. Using ICD code J84.2, we identified patients with a diagnosis of LIP, and further selected for those who had undergone PET/CT between 2009 and 2023. We analyzed descriptive statistics, including the mean and prevalence of common PET/CT findings. Results: We identified 10 patients, all of whom had anestablished expert diagnosis of LIP and had undergone PET/CT for any reason. The mean age was 66 years, and all patients were female. Six of the ten patients (60%) underwent a lung biopsy, and six (60%) exhibited FDG uptake in the lungs, with maximum standard uptake value (SUVmax) uptake ranging from 2.0 to 8.2. Six of the imaging studies (60%) showed abnormal FDG uptake in one or more lymph nodes, with SUV maximum ranging from 2.4 to 7.8, and four (40%) demonstrated extrapulmonary FDG uptake. Four patients were diagnosed with a malignancy, the majority being MALT, with one being lung squamous cell carcinoma (SCC). Conclusion: Given the rarity of LIP, there is limiteddata on the utility and findings of PET/CT in these patients. Our study reveals that in patients with LIP, despite abnormal parenchyma in the background of inflammatory disease, malignancy was still likely in abnormally hypermetabolic regions. In this study, lymphoma was the most common malignancy isolated in patients with LIP. Nonetheless, malignancy other than lymphoma can occur, namely squamous cell carcinoma (SCC), and PET positivity can occur in LIP patients even in the absence of tissue proven malignancy. In patients with LIP, SUVmax does not appear to be a differentiating factor between those later diagnosed with lymphoma (SUVmax 2.0-8.2) and SCC (SUVmax=3.1).