Citations

Abstract Rationale Endobronchial valve (EBV) placement is an established bronchoscopic lung volume reduction (BLVR) therapy for advanced emphysema. Although randomized trials have shown improvements in lung function, real-world data on predictors of response and complications remain limited. This study evaluated physiological and clinical outcomes after EBV placement and explored predictors of treatment response and adverse events. Methods We retrospectively analyzed 75 patients who underwent EBV placement for severe emphysema at Mayo Clinic Florida between 2018 and 2023. Demographics, comorbidities, pulmonary function test and complications data were collected before and after procedure. Responders were defined as those achieving a ≥ 15% relative increase in forced expiratory volume in one second (FEV1), ≥10% reduction in residual volume (RV), ≥25-meter increase in six-minute walk distance (6MWD), or ≥ 1-point decrease in modified Medical Research Council (mMRC) dyspnea score. Results The mean age was 70.4 ± 7.1 years, 59% were female, and the mean Body Mass Index was 25.6 ± 4.9 kg/m². Most patients were non-Hispanic White (96%) and ever-smokers (97%, median 40 pack-years). Following EBV placement, FEV1 increased by + 0.10 L (p < 0.001), forced vital capacity by + 0.17 L (p = 0.001), RV decreased by -0.69 L (p < 0.001), while total lung capacity decreased by -0.35 L (p < 0.001). Diffusing capacity, 6MWD, and mMRC did not significantly change. Responder analysis showed FEV1 improvement in 52% (34/65), RV reduction in 65% (42/65), 6MWD gain in 33% (18/55), and mMRC improvement in 33% (21/63). Complete lobar atelectasis occurred in 59% (44/75) and was significantly associated with FEV1 improvement (p < 0.01). 30-day follow up complications included pneumothorax (26.7%), COPD exacerbation (21%), and pneumonia (20%). 15% pneumothoraces were managed conservatively, 55% required chest tube, 30% needed valve removal due to persistent air leak. Valve migration and replacement occurred in 2.6% each, and valve removal in 26.6% patients. Median hospital stay was longer in patients with complications (5 vs 4 days, p = 0.003). In-hospital mortality was 5.3% but no procedure-related deaths were identified. Conclusions EBV placement is a safe and effective BLVR approach yielding significant improvements in FEV1 and reductions in hyperinflation. Pneumothorax and valve-related events were the most frequent complications. Complete lobar atelectasis strongly correlated with functional improvement, suggesting that early reassessment should be considered when collapse is not achieved to prevent complications and unnecessary valve retention. This abstract is funded by: None

Abstract Primary Ciliary Dyskinesia (PCD) is a rare, genetically heterogenous disorder of motile cilia, leading to impaired mucociliary clearance and chronic respiratory disease. Its clinical presentation often overlaps with common conditions, including obstructive pulmonary diseases, contributing to diagnostic delays. Mutations in the DNAH11 gene are associated with PCD, but patients frequently lack the classic ultrastructural ciliary defects. We present a case which highlights the importance of considering rare ciliopathies in patients with refractory respiratory symptoms and the evolving role of genetic testing in diagnosis. A 44-year-old woman with early onset asthma was referred for evaluation of recurrent pneumonias, occurring biannually in recent years. She had been affected by respiratory disease since childhood. Despite aggressive asthma management, including long-term mepolizumab, she reported frequent pneumonias and persistent respiratory symptoms. Pulmonary function tests demonstrated obstructive physiology with bronchodilator responsiveness. Chest CT revealed diffuse cylindrical bronchiectasis, small airway disease, and a tree-in-bud pattern. Initial genetic testing identified heterozygous variants in DNAH11 and AP3D1. Whole genome sequencing later revealed a maternally inherited, likely pathogenic, DNAH11 variant and a paternally inherited variant of uncertain significance (VUS), suggesting a compound heterozygous state. Although not definitively diagnostic, this genetic profile, combined with lifelong respiratory symptoms, and imaging findings, raised strong clinical suspicion for PCD. She was treated targeting both asthma and PCD. Her regimen included a combination inhaler of fluticasone, umeclidinium, and vilanterol, as-needed albuterol, mepolizumab, and the addition of airway clearance focused techniques, including nebulized hypertonic saline, flutter valves, and chest physiotherapy. She demonstrated significant symptomatic improvement and a dramatic reduction in pneumonias or exacerbations. This case underscores the diagnostic complexity of chronic respiratory disease in young adults. PCD should be considered in patients with early-onset, persistent respiratory symptoms and recurrent infections, particularly when standard asthma therapies fail. DNAH11 mutations are known to cause PCD, often without detectable ciliary ultrastructural abnormalities, making diagnosis reliant on clinical features, nasal nitric oxide levels, high-speed video microscopy, and genetic testing. Compound heterozygosity involving a pathogenic variant and a VUS, as seen in this case, is not definitively diagnostic per current ATS/ERS guidelines, but may support a clinical diagnosis when aligned with phenotype and imaging findings. This case illustrates the importance of a multidisciplinary approach, including pulmonology, allergy, genetics, and immunology, in evaluating complex respiratory presentations. Early recognition and tailored therapy, including airway clearance and infection prevention, are critical to improving patient outcomes and quality of life in patients with suspected PCD. This abstract is funded by: None

Background: Sepsis survivors experience substantial long-term cardiovascular (CV) morbidity and mortality. The pooled-cohort atherosclerotic cardiovascular disease (ASCVD) score estimates 10-year risk in the general population, but its accuracy soon after sepsis is unknown. Objectives: (1) Describe the absolute five-year incidence of major adverse cardiovascular events (MACE) after sepsis hospitalization. (2) Evaluate the discrimination and calibration of the 10-year ASCVD score for predicting five-year MACE in this setting. Research Questions: The ASCVD score would underpredict five-year MACE in sepsis survivors, reflecting their heightened risk. Methods: We performed a retrospective closed-cohort study using electronic health records from Mayo Clinic hospitals (USA). Adults aged 40–75 years hospitalized for sepsis between 2018 and 2020 were eligible if follow-up was ≥5 years; the age criterion matched the derivation range of the ASCVD score. The primary outcome was five-year MACE—myocardial infarction (MI), ischemic or hemorrhagic stroke, or CV death. Secondly we evaluated the predictive performance of ASCVD score for five-year MACE. Discrimination was assessed with the area under the receiver-operating curve (AUROC); calibration with Calibration-in-the-Large (CITL, ideal = 0) and slope (ideal = 1). Performance metrics were calculated in patients with complete ASCVD variables. Results: A total of 6306 sepsis admissions were screened. 2424 patients were excluded for age outside 40–75 years and 879 for <5 year follow-up, leaving 2718 patients for incidence analyses. Median age was 65 years (IQR 56–70); 55 % were male, 38 % required ICU care, and 91 % were White. Median body-mass index was 28.2 kg/m2 (IQR 23.7-34.7). During follow-up, 125 patients (4.6 %) had MI, 219 (8.1 %) experienced stroke, and 303 (11.1 %) died of CV causes; overall, 1573 patients (57.9 %) met the composite MACE outcome. Complete ASCVD data were available for 409 patients. In this subset, discrimination was moderate (AUROC 0.65; 95 % CI 0.59–0.71). Calibration showed CITL +0.34 (95 % CI 0.09–0.59) and slope 0.50 (95 % CI 0.28–0.72), indicating systematic infra-prediction and over-fitting, respectively. Conclusion: Five-year MACE incidence after sepsis is high. The 10-year ASCVD score moderately discriminates but underestimates five-year CV risk in this population, highlighting the need for sepsis-specific predictive models or recalibration to guide targeted post-sepsis cardiovascular prevention.

Abstract Rationale: The D'Nerva Targeted Lung Denervation (TLD) System uses radiofrequency energy delivered bronchoscopically to the main bronchi to disrupt parasympathetic nerve innervation to the lung. AIRFLOW-3 clinical trial was a randomized, double blind, sham controlled study to determine the impact of TLD on COPD exacerbations. Methods: AIRFLOW-3 patients had symptomatic COPD (CAT ≥10) with moderate to very severe airflow obstruction (GOLD stage II-IV: 25% ≤ FEV1 ≤ 80% predicted, FEV1/FVC&lt;0.70) and GOLD E status (≥2 moderate or ≥1 severe exacerbation in the prior 12 months) despite optimal medical therapy. The primary endpoint was a time-to-first event comparison of the probability of subjects having a moderate or severe exacerbation, between the Treatment arm (TLD + optimal medical therapy) and the Sham Control arm (optimal medical therapy). Results: 388 patients were randomized 1:1 at 32 clinical sites across the US, EU, and UK. Patients were 67.8 (SD 7.1) years of age, ex-smokers with a 46.7 (22.0) pack-year smoking history, and 41.0 (11.8) post bronchodilator FEV1% pred. SGRQ-C and CAT scores were 62.5 (17.0) and 23.6 (6.3), respectively. Over 90% of patients were on triple therapy (LAMA+LABA+ICS) at baseline and through 1 year of follow up. 42% of patients had prior-year COPD hospitalization(s). There was no difference between groups in the analysis of the primary endpoint. At 1 year, the sham arm exhibited a statistical decline in lung function (decrease in FEV1 and FVC) and worsening of gas trapping (increase in RV). Lung function and gas trapping were stable in the treatment arm. The treatment arm exhibited a statistically significant improvement in dyspnea at one year compared to sham (mMRC, and TDI). These observations led to the identification of a subgroup of TLD treatment responders corresponding to an airway predominant phenotype (lung hyperinflation in the absence of significant emphysema) that demonstrated clinically and statistically significant improvements in lung function and exacerbation frequency and severity (Table). Conclusions: The AIRFLOW-3 clinical trial failed to meet its prespecified primary endpoint. Post-hoc analysis of this robust dataset led to the identification of a responder profile that achieved significant and sustained improvements in lung function, and exacerbation reduction. A future clinical study is being designed to confirm these findings.

Abstract Introduction: Trastuzumab emtansine (T-DM1) is a standard therapeutic agent for advanced stages of HER2-positive breast cancer, known to improve survival rates. However, it is associated with side effects including fatigue, anemia, and mild-to-moderate bleeding. We present a rare case of pulmonary arteriovenous malformations (PAVMs) potentially linked to T-DM1 therapy, with clinical manifestations resembling hereditary hemorrhagic telangiectasia (HHT). Case Presentation: A 57-year-old female presented with chronic hypoxia on 3 L/min nasal oxygen. Her history included two years of worsening exertional dyspnea and hypoxemia during T-DM1 therapy for HER2-positive breast cancer, diagnosed 10 years earlier. She underwent bilateral mastectomy and was treated with T-DM1 and anastrozole. Echocardiography suggested a right-to-left shunt, while right heart catheterization excluded pulmonary hypertension. Subsequent CT angiography revealed small peripheral PAVMs, confirmed by Tc-99m MAA scintigraphy with a 30% right-to-left shunt. Lab results showed PaO2 at 52 mmHg, HCO3 at 20.3 mmol/L, O2 saturation at 86.4%, and PCO2 at 31 mmHg. Pulmonary function tests indicated restrictive lung volumes and severe diffusion impairment (FVC: 2.66 L, FEV1: 2.06 L, FEV1/FVC: 77.5%, TLC: 3.99 L, DLCO-SB: 20.7% predicted). Following discontinuation of T-DM1, patient experienced slight improvement in telangiectasias and dyspnea over three months but continued to require 10-15 L/min of oxygen during exertion. Arterial blood gas analysis showed a PaO2 of 56.4 mmHg, HCO3 of 20.7 mmol/L, resting O2 saturation of 88.4%, PCO2 of 26.8 mmHg, and PaO2 of 180.9 mmHg on 100% oxygen via a non-rebreather mask, indicating a persistent right-to-left shunt. Discussion: Arteriovenous malformations (AVMs) are abnormal artery-vein connections linked to HHT, with PAVMs present in 80-90% of HHT cases, leading to right-to-left shunts. This patient's prolonged T-DM1 therapy appears associated with PAVMs and HHT-like symptoms. While T-DM1 has been linked to pulmonary and portal hypertension, as well as cerebral AVMs, this is the first report associating it with PAVMs, possibly through disruption of endothelial function and HHT pathways like ALK1 and ENG. Diagnosing PAVMs can be challenging due to their often-asymptomatic nature; however, in this case, they were identified through repeated CT imaging and Tc-99m MAA scintigraphy. Embolization, a typical intervention for PAVMs, was not feasible due to the small size of the malformations. The patient's condition improved after discontinuing T-DM1, suggesting a potential link between the drug and PAVMs. Understanding the mechanisms by which T-DM1 induces vascular abnormalities is crucial for developing targeted interventions and improving patient outcomes.

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).

Pulmonary embolic disease is most commonly a manifestation of venous thromboembolism (VTE). However, fat, tumor, and air may all embolize to the pulmonary vasculature and lymphatics resulting in various clinical manifestations. Tumor emboli to small pulmonary vessels and lymphatics can lead to hypoxemic respiratory failure and shock. We present a 62-year-old male with history of mild COPD and end-stage liver disease secondary to hepatitis C admitted due to progressive shortness of breath and hypoxemia who developed shock and right ventricular failure. After a negative evaluation for venous thromboembolic disease, he had progressive respiratory and hemodynamic deterioration despite mechanical ventilation, renal replacement therapy, and vasopressive/inotropic support. Postmortem examination revealed diffuse micronodular moderately differentiated hepatocellular carcinoma (HCC) without a discrete mass, as well as numerous HCC tumor emboli to the lung and focally to the heart, consistent with disseminated hepatocellular tumor microembolism.

A 47-year-old Hispanic woman developed a chronically obstructed left kidney, due to a long-segment ureteric stricture deemed not amenable to reimplantation, following left ovarian cyst excision in 2004. Therefore, a ureteral stent requiring exchange every 3 months was necessary, due to hydronephrosis, recurrent urosepsis, chronic pain, and a poor quality of life. Her medical history was complicated by hypertension, poorly controlled diabetes mellitus, and microalbuminuria, suggesting early diabetic nephropathy. A left nephrectomy was recommended. This was deferred, due to concern for progressive kidney failure associated with her comorbidities. A radionuclide Tc-99m MAG3 renal scan revealed differential perfusion as follows: 44% left kidney and 56% right kidney, with symmetrical uptake on the renogram phase and delayed excretion on the left, which were correctted following furosemide administration. A left ureteronephrectomy with autotransplantation of the left kidney and ureteroneocystostomy was performed in 2009. Since then, the patient has experienced no further complications or need for invasive procedures, with excellent diabetic control and stable renal function (eGFR > 60 mL/min/1.73 m2). This technique is seldom employed in the surgical management of complex ureteral injuries, but may be an alternative for appropriate cases.