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Interstitial lung disease (ILD) is a frequent manifestation of rheumatoid arthritis (RA) that is associated with high mortality. RA‐ILD may initially be asymptomatic, and lung function may be markedly impaired by the time it is diagnosed. The course of RA‐ILD is highly variable, with some patients experiencing no discernable progression or a slow decline, whereas others experience more rapid deterioration. Some patients develop progressive pulmonary fibrosis, which is associated with high mortality. Although risk factors for the progression of RA‐ILD have been identified, including older age, worse lung function, and a usual interstitial pneumonia pattern on high‐resolution computed tomography, it is not possible to predict the course of RA‐ILD in an individual patient. The association between RA disease activity and progression of RA‐ILD remains unclear. Regular monitoring is important to enable the prompt identification of progression and early intervention to preserve lung function. The management of RA‐ILD requires a multidisciplinary and individualized approach, taking account of the severity and progression of articular and lung disease, risk factors for the progression of RA‐ILD, and the patient's preferences, and may include immunosuppression, antifibrotic therapy, and supportive care.

ABSTRACTBackgroundEvolving trends in organ procurement and technological innovation prompted an investigation into recent trends, indications, and outcomes following combined heart–lung transplantation (HLTx).MethodsThe United Network for Organ Sharing database was queried for all adult (≥18 years) HLTx performed between July 1, 2013 and June 30, 2023. Patients with previous transplants were excluded. The primary endpoint was the effect of donor, recipient, and transplantation characteristics on 1‐ and 5‐year survival. Secondary analyses included a comparison of HLTx at high‐ and low‐volume centers, an assessment of HLTx following donation after circulatory death (DCD), and an evaluation of HLTx volume over time. Cox proportional‐hazards models were used to assess factors associated with mortality. Temporal trends were evaluated with linear regression.ResultsAfter exclusions, 319 patients were analyzed, of whom 5 (1.6%) were DCD. HLTx volume increased from 2013 to 2023 (p < 0.001). One‐ and 5‐year survival following HLTx was 84.0% and 59.5%, respectively. One‐year survival was higher for patients undergoing HLTx at a high‐volume center (88.3% vs. 77.9%; p = 0.012). After risk adjustment, extracorporeal membrane oxygenation support 72 h posttransplant and predischarge dialysis were associated with increased 1‐year mortality (HR = 3.19, 95% CI = 1.86–5.49 and HR = 3.47, 95% CI = 2.17–5.54, respectively) and 5‐year mortality (HR = 2.901, 95% CI = 1.679–5.011 and HR = 3.327, 95% CI = 2.085–5.311, respectively), but HLTx at a high‐volume center was not associated with either.ConclusionsHLTx volume has resurged, with DCD HLTx emerging as a viable procurement strategy. Factors associated with 1‐ and 5‐year survival may be used to guide postoperative management following HLTx.

AimTransbronchial cryobiopsies are increasingly used for the diagnosis of interstitial lung disease (ILD), but there is a lack of published information on the features of specific ILD in cryobiopsies. Here we attempt to provide pathological guidelines for separating usual interstitial pneumonia (UIP) of idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (FHP) and connective tissue disease‐associated ILD (CTD–ILD) in cryobiopsies.MethodsWe examined 120 cryobiopsies from patients with multidisciplinary discussion (MDD)‐established CTD–ILD and compared them to a prior series of 121 biopsies from patients with MDD‐established IPF or FHP.ResultsA non‐specific interstitial pneumonia (NSIP) pattern alone was seen in 36 of 120 (30%) CTD–ILD, three of 83 (3.6%) FHP and two of 38 (5.2%) IPF cases, statistically favouring a diagnosis of CTD–ILD. The combination of NSIP + OP was present in 29 of 120 (24%) CTD–ILD, two of 83 (2.4%) FHP and none of 38 (0%) IPF cases, favouring a diagnosis of CTD–ILD. A UIP pattern, defined as fibroblast foci plus any of patchy old fibrosis/fibrosis with architectural distortion/honeycombing, was identified in 28 of 120 (23%) CTD–ILD, 45 of 83 (54%) FHP and 27 of 38 (71%) IPF cases and supported a diagnosis of FHP or IPF. The number of lymphoid aggregates/mm2 and fibroblast foci/mm2 was not different in IPF, CTD–ILD or FHP cases with a UIP pattern. Interstitial giant cells supported a diagnosis of FHP or CTD–ILD over IPF, but were infrequent.ConclusionsIn the correct clinical/radiological context the pathological findings of NSIP, and particularly NSIP plus OP, favour a diagnosis of CTD–ILD in a cryobiopsy, but CTD–ILD with a UIP pattern, FHP with a UIP pattern and IPF generally cannot be distinguished.

The lung is an inherently mechanosensitive organ that can respond to mechanical forces in adaptive or maladaptive ways, including via remodeling resulting in increased fibrosis. We explored the mechanisms that link mechanical forces to remodeling using human lung fibroblasts. We found that mechanosensitive Piezo channels increase with stretch and mediate extracellular matrix formation and the fibroblast-to-myofibroblast transition that occurs with stretch. Our data highlight the importance of Piezo channels in lung mechanotransduction toward remodeling.

Introduction: Recipients of lung transplants are at heightened risk of developing low bone mineral density (BMD). They also have increased risk of developing osteoporosis-related fractures. This rate of BMD decline is not well characterized. The aim of this manuscript is to characterize the rate of BMD decrease after lung transplant. Methodology: This is a preliminary retrospective cohort study of 200 patients who received lung transplants. Each patient had pre-transplant dual energy X-ray absorptiometry (DXA) and post-transplant DXA scans on the same DXA scanner. The BMD at each lumbar vertebra, total hip, and femoral neck were recorded. Generalized linear mixed effects models with random intercepts and random slopes were used to model the rate of change of BMD after transplant, adjusting for time since transplant, sex, and sex*time interaction. Results: We found that men had higher baseline BMD than women at all sites (P<0.05 for all). The rate of BMD decrease was fastest at the femoral neck (P<0.05). Men lost BMD at a faster rate (-5.23 x10-5 g/cm2/day) than women at the femoral neck (-2.22 x10-5 g/cm2 /day). Conclusion: BMD decreases after lung transplant and occurs faster in men than women.

Abstract The Blood and Marrow Transplant (BMT) Clinical Trials Network conducted a phase 3 randomized trial comparing gilteritinib with placebo after allogeneic hematopoietic cell transplantation (HCT) for FLT3-ITD+ acute myeloid leukemia (AML). The primary analysis demonstrated no statistically significant difference in relapse-free survival (RFS); however, patients with FLT3-ITD measurable residual disease (MRD) peri-HCT had significantly longer RFS with gilteritinib. This analysis investigates the effect of post-HCT gilteritinib vs placebo on health-related quality of life (HRQOL). HRQOL was measured with Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), FACT-Leukemia (FACT-Leu), and EuroQOL-5 Dimensions (EQ-5D-5L) at post-HCT randomization; day 29; months 3, 6, 12, 18, 24; and/or end of therapy. HRQOL and clinically meaningful differences were summarized using descriptive statistics and compared using mixed model repeated measures to evaluate longitudinal change from baseline and stratified Cox model to evaluate time to improvement. HRQOL completion rate was acceptable (&gt;70%) across all time points and measures. There were no differences in HRQOL scores at any time point between cohorts. Clinically meaningful and time to improvement in HRQOL were similar in both arms. Despite higher treatment-emergent adverse effects with gilteritinib, response to the question of being “bothered by side effects of treatment” did not differ between groups. Subgroup analysis of MRD-positive and negative patients demonstrated no differences in HRQOL between arms. For patients with FLT3-ITD+ AML undergoing HCT, gilteritinib maintenance was not associated with any difference in HRQOL or patient-reported impact of side effects. This trial was registered at www.ClinicalTrials.gov as #NCT02997202.

Respiratory failure occurs more frequently after thoracic surgery than abdominal surgery. Although the etiology for this complication is frequently attributed to underlying lung disease present in patients undergoing thoracic surgery, this notion is often unfounded because many patients with normal preoperative pulmonary function often require prolonged oxygen supplementation even after minimal resection of lung tissue. Using a murine model of pulmonary resection and peripheral blood samples from patients undergoing resection of the lung or abdominal organs, we demonstrated that lung surgery initiates a proinflammatory loop that results in damage to the remaining lung tissue, noncardiogenic pulmonary edema, hypoxia, and even death. Specifically, we demonstrated that resection of murine lung tissue increased concentrations of the homeostatic cytokine interleukin-7, which led to local and systemic activation of type 2 innate lymphoid cells. This process activated lung-resident eosinophils and facilitated stress-induced eosinophil maturation in the bone marrow in a granulocyte-macrophage colony-stimulating factor–dependent manner, resulting in systemic eosinophilia in both mice and humans. Up-regulation of inducible nitric oxide synthase in lung-resident eosinophils led to tissue nitrosylation, pulmonary edema, hypoxia, and, at times, death. Disrupting this activation cascade at any stage ameliorated deleterious outcomes and improved survival after lung resection in the mouse model. Our data suggest that repurposing US Food and Drug Administration–approved eosinophil-targeting strategies may potentially offer a therapeutic intervention to improve outcomes for patients who require lung resection for benign or malignant etiology.

213 Background: Lung cancer patient often encounter disparities in health outcomes, especially in difference racial and ethnic groups. Metastasis is the primary cause of cancer morbidity and mortality. However, data on the metastasis risks and clinical outcomes on hospitalized individuals with lung cancer is still limited. Therefore, we aim to assess the association between metastatic lung cancer and racial differences. Methods: We analyzed the 2020 U.S. National Inpatient Sample (NIS) to explore patients who have lung cancer as the primary diagnosis. Additionally, we identified evidence of metastasis, as recorded by ICD-10-CM. Adjusted odds ratios (aORs) for specified outcomes were calculated through multivariable logistic and linear regression analyses. The primary outcome was racial differences in organ metastasis and secondary outcomes included mortality and length of stay. Statistical significance was established at p-value of 0.05. Results: We identified 103,335 patients with primary diagnosis of lung and bronchus cancer at discharge. The mean age was 68.9 years; 50.5% were female. Caucasians accounted for 74.3%, with African Americans at 12.1% and Hispanics at 4.6%. 10% of the patients had brain metastasis, whereas 14% had bone metastasis. In a multivariate analysis adjusting for patient, COVID-19, chemotherapy usage and hospital factors, African Americans had higher risk of brain metastasis (aOR 1.18; 95%CI (1.02, 1.37), p = 0.002), higher risk of bone metastasis (aOR 1.16; 95%CI (1.02, 1.33), p = 0.025), higher risk of mortality (aOR 1.21; 95% CI (1.01, 1.45), p = 0.039) and longer length of stay (b = 0.85; 95%CI (0.55, 1.16), p = 0.001). Hispanics also had higher risk of brain (aOR 1.36, p < 0.05) and prolonged length of stay (b 0.79, p < 0.005). We observed an increase in risk of metastasis and mortality but non-statistically significant in some parameters and races, as shown in table provided. Conclusions: In conclusion, our study revealed that racial difference is associated with higher risk of metastasis, as well as other outcomes. Further longitudinal research is necessary to establish a causal relationship between races, metastasis, and mortality in patients with lung cancer. [Table: see text]