Pulmonology Commons^™

Delta-Like Ligand 3 (Dll3) Landscape In Pulmonary And Extra-Pulmonary Neuroendocrine Neoplasms, Alejandra G Serrano, Pedro Rocha, Cibelle Freitas Lima, Allison Stewart, Bingnan Zhang, Lixia Diao, Junya Fujimoto, Robert J Cardnell, Wei Lu, Khaja Khan, Beate Sable, Aaron R Ellison, Ignacio I Wistuba, Kyle F Concannon, Daniel M Halperin, Czerniak Bogdan, Kanishka Sircar, Miao Zhang, Kasey Cargill, Qi Wang, Ana Aparicio, Alexander Lazar, Sharia Hernandez, Jeannelyn Estrella, Preetha Ramalingam, Adel El-Naggar, Neda Kalhor, Carl M Gay, Lauren Averett Byers, Luisa M Solis Soto

Faculty, Staff and Student Publications

Delta-like Ligand 3 (DLL3) targeting therapies are promising in small cell lung cancer (SCLC) treatment. However, DLL3 expression in SCLC and other neuroendocrine neoplasms (NEN) is heterogeneous and not well characterized. We describe the landscape of DLL3 at the mRNA and protein levels across SCLC, large cell neuroendocrine carcinoma (LCNEC), and non-small cell lung cancer. Additionally, we explore its expression in extra-pulmonary NEN (EP-NEN) using a standardized DLL3 IHC assay. DLL3 expression is enriched in SCLC, LCNEC along with combined histology lung cancers. Moreover, we find a wide range of DLL3 expression in high-grade EP-NEN. We describe heterogenous DLL3 expression …

Lung Tissue Multilayer Network Analysis Uncovers The Molecular Heterogeneity Of Chronic Obstructive Pulmonary Disease, Nuria Olvera, Jon Sánchez-Valle, Iker Núñez-Carpintero, Joselyn Rojas-Quintero, Guillaume Noell, Sandra Casas-Recasens, Alen Faiz, Philip Hansbro, Angela Guirao, Rosalba Lepore, Davide Cirillo, Alvar Agustí, Francesca Polverino, Alfonso Valencia, Rosa Faner

Faculty, Staff and Students Publications

Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition. Objectives: We hypothesized that the unbiased integration of different COPD lung omics using a novel multilayer approach might unravel mechanisms associated with clinical characteristics.

Methods: We profiled mRNA, microRNA and methylome in lung tissue samples from 135 former smokers with COPD. For each omic (layer), we built a patient network on the basis of molecular similarity. The three networks were used to build a multilayer network, and optimization of multiplex modularity was used to identify patient communities across the three distinct layers. Uncovered communities were related to clinical features.

Measurements …

Evaluating Tirzepatide's Therapeutic Potential In Mitigating Obesity-Associated Comorbidities, Zaneh Kahook, Talaya Jones, Carina Bryan, Mayur Parmar

HCA-NSU MD Research Day

Objective: The study aims to explore the therapeutic potential of dual GIP/GLP-1 agonist tirzepatide in managing obesity and its associated manifestations, including obstructive sleep apnea (OSA), hidradenitis suppurativa (HS), and obesity-associated cancer (OAC) risks. Background: OSA and HS are the associated comorbidities noted in persons with obesity. Obesity has been associated with an increased risk of cancers, such as breast cancer. Reducing obesity could improve these conditions. Tirzepatide has demonstrated efficacy in reducing body weight, but its benefits in obesity-related conditions and cancer risk need further investigation. Methods: Data was synthesized from peer-reviewed literature on tirzepatide. Additional sources were identified …

The Complex Relationship Between Tuberculosis And Hyperglycemia, Michelle Byers, Elizabeth Guy

Faculty, Staff and Students Publications

Hyperglycemia and tuberculosis are dual global pandemics. Each has a propulsive and amplifying effect on the other, and, because of this, we must consider hyperglycemia and tuberculosis together. Hyperglycemia is immunosuppressive and increases the risk of tuberculosis by threefold. It also leads to a more advanced presentation of pulmonary tuberculosis, thus increasing the likelihood of being smear positive and having cavitating lesions, and it impacts the duration and outcomes of treatment, with an increased one year mortality seen in patients with tuberculosis and diabetes. Additionally, any degree of hyperglycemia can have an impact on susceptibility to tuberculosis, and this effect …

Transcutaneous Electrical Nerve Stimulation For Fibromyalgia-Like Syndrome In Patients With Long-Covid: A Pilot Randomized Clinical Trial, Alejandro Zulbaran-Rojas, Rasha O Bara, Myeounggon Lee, Miguel Bargas-Ochoa, Tina Phan, Manuel Pacheco, Areli Flores Camargo, Syed Murtaza Kazmi, Mohammad Dehghan Rouzi, Dipaben Modi, Fidaa Shaib, Bijan Najafi

Faculty, Staff and Students Publications

This study investigated the effect of Transcutaneous Electrical Nerve Stimulation (TENS) for fibromyalgia-like symptoms including chronic widespread musculoskeletal pain, fatigue, and/or gait impairment in twenty-five individuals with long-COVID. Participants were randomized to a high dose (intervention group, IG) or low dose (placebo group, PG) TENS device. Both groups received daily 3-5 h of TENS therapy for 4-weeks. The Brief Pain Inventory assessed functional interference from pain (BPI-I), and pain severity (BPI-S). The global fatigue index (GFI) assessed functional interference from fatigue. Wearable technology measured gait parameters during three 30-feet consecutive walking tasks. At 4-weeks, the IG exhibited a greater decrease …

Pulmonary Artery Stenting In Cancer Patients: A Single-Center Experience, Jay Gupta, Ronak Patel, Neal Patel, David Wynne, Mohammad Ghasemi-Rad

Faculty, Staff and Students Publications

Endovascular stenting of the pulmonary artery treats arterial stenosis from pulmonary hypertension, congenital heart defects, or post-transplant stricture. Patients with malignant extrinsic pulmonary arterial compression, secondary to large mediastinal or pulmonary masses, often present with dyspnea, hypoxemia, and right ventricular failure. Conventional therapies like surgery, chemotherapy, and radiation are often slow and fail to promptly resolve acute symptoms. Balloon angioplasty and stenting have been explored as a rapid treatment to alleviate symptoms of external pulmonary artery compression. Despite its potential, the adoption of this procedure is limited due to risks like stent misplacement, migration, cardiac arrhythmias, and arterial rupture. This …

Access To Treatment For Chronic Obstructive Pulmonary Disease In The Americas: A Call For Action A Joint Perspective From The Brazilian Thoracic Society, Canadian Thoracic Society, Latin American Thoracic Society, And The American Thoracic Society, Francesca Polverino, Mohit Bhutani, Gustavo Zabert, Frederico Leon Arrabal Fernandes, Karen Czischke, Luiz Fernando Pereira Ferreira, Lian Szabo, Juan P Wisnivesky, Margareth Pretti Dalcolmo, Juan C Celedón

Faculty, Staff and Students Publications

Chronic obstructive pulmonary disease (COPD) is a major public health problem in the Americas (a region of the world comprising North, Central, and South America), although there is substantial variation in disease prevalence, morbidity, and mortality between and within nations. Across the Americas, COPD disproportionately affects vulnerable populations, including minoritized populations and impoverished persons, who are more likely to be exposed to risk factors such as tobacco use, air pollution, infections such as tuberculosis, and biomass smoke, but less likely to have adequate healthcare access. Management of COPD can be challenging across the Americas, with some barriers being specific to …

A Rare Case Of Pulmonary Nocardiosis With Pseudomonas Aeruginosa Superinfection In An Immunocompromised Patient, Kevin Liu, Md, Samuel Shulimson, Do, Herbert Patrick, Md

Jefferson Health - Northeast Posters (formerly Aria Health Posters)

Introduction

Nocardiosis is an uncommon opportunistic infection with over two thirds occurring in those who are immunocompromised [1] or who have undergone solid organ transplants [2]. Here, we present a unique case of pulmonary Nocardiosis complicated by superimposed Pseudomonas infection.

Personalized Copd Care: The Future Of Precision-Based Therapies, Leslie K Appleton, Nicola A Hanania, Muhammad Adrish

Faculty, Staff and Students Publications

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory illness characterized by long-standing respiratory symptoms and airflow limitation. It is a major contributor to respiratory disease-related deaths and currently ranked as the sixth leading cause of mortality in the United States. Approved pharmacological therapies for the stable disease primarily consist of inhaled short and long-acting bronchodilators, inhaled corticosteroids, azithromycin, and roflumilast. In recent years, significant progress has been made in the management of COPD through the identification of different COPD phenotypes and endotypes, which allows for a more personalized treatment approach. While earlier studies investigating targeted therapies were less promising, …

Sdeper: A Hybrid Machine Learning And Regression Method For Cell-Type Deconvolution Of Spatial Barcoding-Based Transcriptomic Data, Yunqing Liu, Ningshan Li, Ji Qi, Gang Xu, Jiayi Zhao, Nating Wang, Xiayuan Huang, Wenhao Jiang, Huanhuan Wei, Aurélien Justet, Taylor S Adams, Robert Homer, Amei Amei, Ivan O Rosas, Naftali Kaminski, Zuoheng Wang, Xiting Yan

Faculty, Staff and Students Publications

Spatial barcoding-based transcriptomic (ST) data require deconvolution for cellular-level downstream analysis. Here we present SDePER, a hybrid machine learning and regression method to deconvolve ST data using reference single-cell RNA sequencing (scRNA-seq) data. SDePER tackles platform effects between ST and scRNA-seq data, ensuring a linear relationship between them while addressing sparsity and spatial correlations in cell types across capture spots. SDePER estimates cell-type proportions, enabling enhanced resolution tissue mapping by imputing cell-type compositions and gene expressions at unmeasured locations. Applications to simulated data and four real datasets showed SDePER's superior accuracy and robustness over existing methods.

Association Between Neuromuscular Blocking Agents And Outcomes Of Emergency Tracheal Intubation: A Secondary Analysis Of Randomized Trials, Stephanie C. Demasi, Wesley H. Self, Neil R. Aggarawal, Michael D. April, Luke Andrea, Christopher R. Barnes, Jason Brainard, Veronika Blinder, Alon Dagan, Brian Driver, Kevin C. Doerschug, Ivor Douglas, Matthew Exline, Daniel G. Fein, John P. Gaillard, Sheetal Gandotra, Kevin W. Gibbs, Adit A. Ginde, Stephen J. Halliday, Jin H. Han, Taylor Herbert, Kevin High, Christopher G. Hughes, Akram Khan, Andrew J. Latimer, Amelia W. Maiga, Steven H. Mitchell, Derek J. Vanderhaar, James E. Walker, Et Al

School of Medicine Faculty Publications

Study objective: To examine the association between the neuromuscular blocking agent received (succinylcholine versus rocuronium) and the incidences of successful intubation on the first attempt and severe complications during tracheal intubation of critically ill adults in an emergency department (ED) or ICU. Methods: We performed a secondary analysis of data from 2 multicenter randomized trials in critically ill adults undergoing tracheal intubation in an ED or ICU. Using a generalized linear mixed-effects model with prespecified baseline covariates, we examined the association between the neuromuscular blocking agent received (succinylcholine versus rocuronium) and the incidences of successful intubation on the first attempt …

Trβ Activation Confers At2-To-At1 Cell Differentiation And Anti-Fibrosis During Lung Repair Via Klf2 And Cebpa, Xin Pan, Lan Wang, Juntang Yang, Yingge Li, Min Xu, Chenxi Liang, Lulu Liu, Zhongzheng Li, Cong Xia, Jiaojiao Pang, Mengyuan Wang, Meng Li, Saiya Guo, Peishuo Yan, Chen Ding, Ivan O Rosas, Guoying Yu

Faculty, Staff and Students Publications

Aberrant repair underlies the pathogenesis of pulmonary fibrosis while effective strategies to convert fibrosis to normal regeneration are scarce. Here, we found that thyroid hormone is decreased in multiple models of lung injury but is essential for lung regeneration. Moreover, thyroid hormone receptor α (TRα) promotes cell proliferation, while TRβ fuels cell maturation in lung regeneration. Using a specific TRβ agonist, sobetirome, we demonstrate that the anti-fibrotic effects of thyroid hormone mainly rely on TRβ in mice. Cellularly, TRβ activation enhances alveolar type-2 (AT2) cell differentiation into AT1 cell and constrains AT2 cell hyperplasia. Molecularly, TRβ activation directly regulates the …

Multiregional Transcriptomic Profiling Provides Improved Prognostic Insight In Localized Non-Small Cell Lung Cancer, Chenyang Li, Thinh T Nguyen, Jian-Rong Li, Xingzhi Song, Junya Fujimoto, Latasha Little, Curtis Gumb, Chi-Wan B Chow, Ignacio I Wistuba, Andrew P Futreal, Jianhua Zhang, Shawna M Hubert, John V Heymach, Jia Wu, Christopher I Amos, Jianjun Zhang, Chao Cheng

Faculty, Staff and Student Publications

Lung Cancer remains the leading cause of cancer deaths in the USA and worldwide. Non-small cell lung cancer (NSCLC) harbors high transcriptomic intratumor heterogeneity (RNA-ITH) that limits the reproducibility of expression-based prognostic models. In this study, we used multiregional RNA-seq data (880 tumor samples from 350 individuals) from both public (TRACERx) and internal (MDAMPLC) cohorts to investigate the effect of RNA-ITH on prognosis in localized NSCLC at the gene, signature, and tumor microenvironment levels. At the gene level, the maximal expression of hazardous genes (expression negatively associated with survival) but the minimal expression of protective genes (expression positively associated with …

Multi-Ancestry Gwas Meta-Analyses Of Lung Cancer Reveal Susceptibility Loci And Elucidate Smoking-Independent Genetic Risk, Bryan R Gorman, Sun-Gou Ji, Michael Francis, Anoop K Sendamarai, Yunling Shi, Poornima Devineni, Uma Saxena, Elizabeth Partan, Andrea K Devito, Jinyoung Byun, Younghun Han, Xiangjun Xiao, Don D Sin, Wim Timens, Jennifer Moser, Sumitra Muralidhar, Rachel Ramoni, Rayjean J Hung, James D Mckay, Yohan Bossé, Ryan Sun, Christopher I Amos, Va Million Veteran Program, Saiju Pyarajan

Faculty, Staff and Student Publications

Lung cancer remains the leading cause of cancer mortality, despite declining smoking rates. Previous lung cancer GWAS have identified numerous loci, but separating the genetic risks of lung cancer and smoking behavioral susceptibility remains challenging. Here, we perform multi-ancestry GWAS meta-analyses of lung cancer using the Million Veteran Program cohort (approximately 95% male cases) and a previous study of European-ancestry individuals, jointly comprising 42,102 cases and 181,270 controls, followed by replication in an independent cohort of 19,404 cases and 17,378 controls. We then carry out conditional meta-analyses on cigarettes per day and identify two novel, replicated loci, including the 19p13.11 …

Issue 11: Pulmonary & Critical Care Insider, Bharat Bajantri Md, Sarah Ellsworth-Hoffman Mls, Dustin D. Linn Pharmd, Payal Shukla Md, Ms, Patricia Rich Md, Morgan Crites Np-C

Critical Care & Pulmonary

Pulmonary & Critical Care Insider Issue 11

Compiled by Bharat Bajantri, MD, and librarian Sarah Ellsworth, MLS for the clinicians of the Pulmonary and Critical Care team of Parkview.

The Pulmonary & Critical Care Insider newsletter was created by Dr. Bharat Bajantri, MD and Sarah Ellsworth, MLS in 2023 as a form of current awareness for current practice at our hospital, Parkview Health.

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Topics:

VIEWPOINTS:

Blood Pressure Measurement

Home Noninvasive Ventilation

ORIGINAL STUDY SUMMARY

Acute Pulmonary Embolism

The PEXIVAS trial

Respiratory Failure in hemorrhagic shock

SNAPSHOTS:

RBC Transfusions

New Small cell lung cancer Treatment.

Pparγ/Etv2 Axis Regulates Endothelial-To-Mesenchymal Transition In Pulmonary Hypertension, Dong Hun Lee, Minseong Kim, Sarah S Chang, Raham Lee, Andrew J Jang, Juyoung Kim, Jing Ma, Michael J Passineau, Raymond L Benza, Harry Karmouty-Quintana, Wilbur A Lam, Benjamin T Kopp, Roy L Sutliff, C Michael Hart, Changwon Park, Bum-Yong Kang

Faculty, Staff and Student Publications

Endothelial-to-mesenchymal transition (EndoMT) plays an important role in pulmonary hypertension (PH) but the molecular mechanisms regulating EndoMT remain to be defined. We demonstrate that the axis of the transcription factors PPARγ (Peroxisome Proliferator-Activated Receptor gamma) and ETV2 (ETS variant 2) play important roles in the pathogenesis of PH. Decreased levels of the expression of PPARγ and ETV2 along with reduced endothelial and increased EndoMT markers are consistently observed in lungs and pulmonary artery endothelial cells (PAECs) of idiopathic pulmonary arterial hypertension patients, in hypoxia-exposed mouse lungs, human PAECs, and in induced-EndoMT cells. Etv2 +/- mice spontaneously developed PH and right …

Persistent Microbial Infections And Idiopathic Pulmonary Fibrosis – An Insight Into Non-Typeable Haemophilus Influenza Pathogenesis, Dong Hun Lee, Minseong Kim, Sarah S Chang, Raham Lee, Andrew J Jang, Juyoung Kim, Jing Ma, Michael J Passineau, Raymond L Benza, Harry Karmouty-Quintana, Wilbur A Lam, Benjamin T Kopp, Roy L Sutliff, C Michael Hart, Changwon Park, Bum-Yong Kang

Faculty, Staff and Student Publications

Endothelial-to-mesenchymal transition (EndoMT) plays an important role in pulmonary hypertension (PH) but the molecular mechanisms regulating EndoMT remain to be defined. We demonstrate that the axis of the transcription factors PPARγ (Peroxisome Proliferator-Activated Receptor gamma) and ETV2 (ETS variant 2) play important roles in the pathogenesis of PH. Decreased levels of the expression of PPARγ and ETV2 along with reduced endothelial and increased EndoMT markers are consistently observed in lungs and pulmonary artery endothelial cells (PAECs) of idiopathic pulmonary arterial hypertension patients, in hypoxia-exposed mouse lungs, human PAECs, and in induced-EndoMT cells. Etv2 +/- mice spontaneously developed PH and right …

Molecular Landscape Of Erbb2 Alterations In 3000 Advanced Nsclc Patients, Lingzhi Hong, Sonia Patel, Leylah M Drusbosky, Yuanyuan Xiong, Rongrong Chen, Ruixuan Geng, Simon Heeke, Monique Nilsson, Jia Wu, John V Heymach, Yingyi Wang, Jianjun Zhang, Xiuning Le

Faculty, Staff and Student Publications

ERBB2 (HER2) represents a newly recognized actionable oncogenic driver in non-small cell lung cancer (NSCLC), with approved targeted therapy available. Understanding the landscape of ERBB2 alterations and co-occurring mutations is essential for guiding treatment decisions. We conducted an analysis involving 3000 NSCLC patients with all types of ERBB2 alterations, drawn from two extensive retrospective cohorts: 1281 from Geneplus (Chinese) and 1719 from Guardant360 (the United States, US). The incidence of all types of ERBB2 alterations was found to be 5.6% in the Chinese group and 5.2% in the US group. In both cohorts, among oncogenic alterations of ERBB2, exon 20 …

Peran Pemeriksaan Penanda Tumor Cairan Pleura Dalam Diagnosis Efusi Pleura Maligna Akibat Kanker Paru Primer, Cleopas M. Rumende, Noorwati Sutandyo, Arif R. Hanafi, Samuel K. Rumende, Erwin C. Susanto, Truely P. Sitorus

Jurnal Penyakit Dalam Indonesia

Introduction. Pleural effusion is a frequently acquired lung disorder and based on the type of cause it is divided into malignant and non-malignant pleural effusion. Cytological examination of pleural fluid to differentiate between malignant and non-malignant pleural effusion shows varying sensitivity. Research regarding the benefits of CEA and Cyfra 21-1 pleural fluid examination to detect malignant pleural effusion due to primary lung cancer in Indonesia is still very limited. The aims of this study is to determine the sensitivity and specificity of CEA and Cyfra 21-1 pleural fluid in diagnosing malignant pleural effusion due to primary lung camcer.

Methods …

Ventilasi Noninvasif Pada Obstructive Sleep Apnea Dan Obesity Hypoventilation Syndrome, Herikurniawan Herikurniawan, Joanna Audrey, Firina Adelya

Jurnal Penyakit Dalam Indonesia

Chronic respiratory disease such as obstructive sleep apnea (OSA) and obesity-hypoventilation syndrome (OHS) remain are respiratory sleeping disorder that gradually affect quality of life. Comprehensive treatment such as the use of non-invasive ventilation (NIV) is a method adopted to improve the patient’s quality of life. The correct choice of NIV mode, mask and titration methods will provide optimal therapeutic effects to the patient. This article review lays out an update on the use of non-invasive ventilation as the treatment of OSA and OHS.