Pulmonology Commons^™

A Commonly Misdiagnosed Rare Pulmonary Disease: Idiopathic Pleuroparenchymal Fibroelastosis, Yonas Raru, Amro K. Al-Astal, Saroj Sigdel

Marshall Journal of Medicine

Awareness among clinicians about Idiopathic pleuroparenchymal fibroelastosis (PPFE) is lacking and by the time patients are diagnosed with it, they were seen by multiple physicians and misdiagnosed multiple times. It is a rare condition that is characterized by fibrosis of the pleura and subpleural lung parenchyma, predominantly affecting the upper lobes. Most common cause of fibrosis in other processes is collagen predominant but in PPFE fibrosis is usually caused by elastic fibers. Verhoeff-Van Gieson stain from lung biopsies in patients who presented with fibrosis in the upper pleural and parenchymal areas will help in establishing the diagnosis by demonstrating the …

Abatacept, Cenicriviroc, Or Infliximab For Treatment Of Adults Hospitalized With Covid-19 Pneumonia: A Randomized Clinical Trial, Jane A O'Halloran, Emily R Ko, Kevin J Anstrom, Eyal Kedar, Matthew W Mccarthy, Reynold A Panettieri, Martin Maillo, Patricia Segura Nunez, Anne M Lachiewicz, Cynthia Gonzalez, P Brian Smith, Sabina Mendivil-Tuchia De Tai, Akram Khan, Alfredo J Mena Lora, Matthias Salathe, Gerardo Capo, Daniel Rodríguez Gonzalez, Thomas F Patterson, Christopher Palma, Horacio Ariza, Maria Patelli Lima, John Blamoun, Esteban C Nannini, Eduardo Sprinz, Analia Mykietiuk, Radica Alicic, Adriana M Rauseo, Cameron R Wolfe, Britta Witting, Jennifer P Wang, Luis Parra-Rodriguez, Tatyana Der, Kate Willsey, Jun Wen, Adam Silverstein, Sean M O'Brien, Hussein R Al-Khalidi, Michael A Maldonado, Richard Melsheimer, William G Ferguson, Steven E Mcnulty, Pearl Zakroysky, Susan Halabi, Daniel K Benjamin, Sandra Butler, Jane C Atkinson, Stacey J Adam, Soju Chang, Lisa Lavange, Michael Proschan, Samuel A Bozzette, William G Powderly, Activ-1 Im Study Group Members

Faculty, Staff and Student Publications

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19.

OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.

DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and …

Neurotropic Manifestations As A Potential Risk Factor For Schizophrenia Following In Utero Exposure To Sars-Cov-2, Mir Ali R Talpur, Omar H. Elsayed, Rif S. El-Mallakh

The University of Louisville Journal of Respiratory Infections

Background: COVID-19 infection is associated with neurologic and psychiatric morbidity that suggests a direct effect of the virus or secondary effect of an inflammatory process. These neuropsychiatric consequences may increase the likelihood of schizophrenia in the offspring of women who become infected with COVID-19 during their pregnancy.

Methods: We performed a directed narrative review of the literature focusing on the proposed pathophysiological processes that lead to schizophrenia and known pathological consequences of COVID-19 infection.

Results: Schizophrenia in adult offspring has been associated with maternal infections during pregnancy by a wide range of respiratory and neurotropic pathogens. Spikes in the incidence …

Randomized, Double-Blinded, Placebo-Controlled Trial Of Allogeneic Cord Blood T-Regulatory Cells For Treatment Of Covid-19 Ards, Douglas E Gladstone, Franco D'Alessio, Christopher Howard, Mi-Ae Lyu, Jason R Mock, Kevin W Gibbs, Darryl Abrams, Meixian Huang, Ke Zeng, James P Herlihy, Sergio T Castillo, Roland Bassett, Tara Sadeghi, Simrit Parmar, Christopher R Flowers, Siddhartha Mukherjee, David Schoenfeld, Peter F Thall, Arthur S Slutsky

Faculty, Staff and Students Publications

No abstract provided.

Emt Activates Exocytotic Rabs To Coordinate Invasion And Immunosuppression In Lung Cancer, Guan-Yu Xiao, Xiaochao Tan, Bertha L Rodriguez, Don L Gibbons, Shike Wang, Chao Wu, Xin Liu, Jiang Yu, Mayra E Vasquez, Hai T Tran, Jun Xu, William K Russell, Cara Haymaker, Younghee Lee, Jianjun Zhang, Luisa Solis, Ignacio I Wistuba, Jonathan M Kurie

Faculty, Staff and Student Publications

Epithelial-to-mesenchymal transition (EMT) underlies immunosuppression, drug resistance, and metastasis in epithelial malignancies. However, the way in which EMT orchestrates disparate biological processes remains unclear. Here, we identify an EMT-activated vesicular trafficking network that coordinates promigratory focal adhesion dynamics with an immunosuppressive secretory program in lung adenocarcinoma (LUAD). The EMT-activating transcription factor ZEB1 drives exocytotic vesicular trafficking by relieving Rab6A, Rab8A, and guanine nucleotide exchange factors from miR-148a-dependent silencing, thereby facilitating MMP14-dependent focal adhesion turnover in LUAD cells and autotaxin-mediated CD8

Professionalism And Moral Injury In A Capitalist Healthcare System, James Peter Meza Md, Phd, Kassem Soufan Md, Michael Francis Do, Abbass Berjaoui Md

Clinical Research in Practice: The Journal of Team Hippocrates

Professionalism cautions against profit while capitalism exists for profit. This case is a structural analysis of capitalism in a clinical setting that reveals physicians to be simultaneously wage laborers and professionals. Capitalism generates profit. Professionalism views profit as a conflict of interest that erodes trust in the doctor-patient relationship. Managing these conflicting values causes moral injury for physicians, which is a driver of physician burnout.

Mechanical Thrombectomy For Intermediate Risk Pulmonary Embolism, James Peter Meza, Marissa Costello Md, Angela Moughni Md, Nicholus Yee Md

Clinical Research in Practice: The Journal of Team Hippocrates

An informed consent article using a set of publications to develop an informed consent conversation for a patient with an acute pulmonary embolism being considered for pulmonary artery thrombolysis.

A Comprehensive Analysis Of Lung Cancer Highlighting Epidemiological Factors And Psychiatric Comorbidities From The All Of Us Research Program, Vikram R Shaw, Jinyoung Byun, Rowland W Pettit, Younghun Han, David A Hsiou, Luke A Nordstrom, Christopher I Amos

Faculty, Staff and Students Publications

Lung cancer is the leading cause of cancer-related mortality in the United States. Investigating epidemiological and clinical parameters can contribute to an improved understanding of disease development and management. In this cross-sectional, case-control study, we used the All of Us database to compare healthcare access, family history, smoking-related behaviors, and psychiatric comorbidities in light smoking controls, matched smoking controls, and primary and secondary lung cancer patients. We found a decreased odds of primary lung cancer patients versus matched smoking controls reporting inability to afford follow-up or specialist care. Additionally, we found a significantly increased odds of secondary lung cancer patients …

Immunotherapy-Related Pneumonitis And The Synergic Impact Of Thoracic Radiation And Preexisting Interstitial Lung Disease, Maria Azhar, Rodeo Abrencillo, Saumil Gandhi, Mehmet Altan, Ajay Sheshadri

Faculty, Staff and Student Publications

PURPOSE OF REVIEW: Immune checkpoint inhibitors (ICIs) are the frontline of therapy for most cancers. Although ICIs are sometimes considered to be less harmful than systemic chemotherapies, ICIs may cause immune-related adverse events, which are cases of off-target inflammation in healthy tissues. Pneumonitis, an immune-related adverse event, is the leading cause of therapy-related mortality with ICIs. The aim of this review is to discuss how preexisting interstitial lung disease (ILD) and thoracic radiation increase the risk for ICI-pneumonitis. We discuss potential mechanisms of lung injury and how pneumonitis may impact cancer treatments.

RECENT FINDINGS: Preexisting ILD and thoracic radiation are …

Multiple Primary Lung Cancers: Treatment Outcomes After Stereotactic Body Radiotherapy (Sbrt), Gyujae Choi, George Chen, Weiyuan Mai, Albert Chen, Angela Zhu

Faculty, Staff and Students Publications

PURPOSE/OBJECTIVES: Patients with lung cancer sometimes present with multiple primary lung cancers (MPLCs), either simultaneously (synchronous) or after treatment of an initial lesion (metachronous). Although open surgery remains a treatment mainstay for patients with stage I-II non-small-cell lung cancer (NSCLC), stereotactic body radiation therapy (SBRT) is an acceptable alternative for patients who are medically unfit for or who refuse surgery. In this study, we retrospectively examine the outcome among patients with early-stage MPLCs treated at our institution with SBRT.

MATERIALS/METHODS: Patients at our institution receiving SBRT for MPLC between June 2011 and March 2020 were reviewed retrospectively. Prior to undergoing …

Plasma Extracellular Vesicle Proteins As Promising Noninvasive Biomarkers For Diagnosis Of Idiopathic Pulmonary Fibrosis, Raju S R Adduri, Kai Cai, Karen Velasco-Alzate, Ravikiran Vasireddy, Jeffrey W Miller, Sergio Poli De Frías, Fernando Poli De Frías, Yasushi Horimasu, Hiroshi Iwamoto, Noboru Hattori, Yingze Zhang, Kevin F Gibson, Anoop K Pal, Zhe Chen, Daniela Nicastro, Li Li, Sujith Cherian, Lynette M Sholl, Sreerama Shetty, Harrison Ndetan, Anthony H Maeda, Maria A Planchart Ferretto, Gary M Hunninghake, David A Schwartz, Daniel J Kass, Ivan O Rosas, Nagarjun V Konduru

Faculty, Staff and Students Publications

High-resolution computed tomography (HRCT) imaging is critical for diagnostic evaluation of Idiopathic Pulmonary Fibrosis (IPF). However, several other interstitial lung diseases (ILDs) often exhibit radiologic pattern similar to IPF on HRCT making the diagnosis of the disease difficult. Therefore, biomarkers that distinguish IPF from other ILDs can be a valuable aid in diagnosis. Using mass spectrometry, we performed proteomic analysis of plasma extracellular vesicles (EVs) in patients diagnosed with IPF, chronic hypersensitivity pneumonitis, nonspecific interstitial pneumonitis, and healthy subjects. A five-protein signature was identified by lasso regression and was validated in an independent cohort using ELISA. The five-protein signature derived …

Calculating Differences In Surrogate Lung Perfusion Measurements Between Smokers And Nonsmokers As A Biomarker To Assess Their Potentials For Developing Chronic Obstructive Pulmonary Disease, A Prakash, A Nowacki, Y K. Liu, J Cisneros-Paz, Girish Nair, E Castillo

Conference Presentation Abstracts

Purpose: COPD (chronic obstructive pulmonary disease) is a collection of lung diseases that complicates breathing and causes irreversible lung damage. Given that it is a progressive disease, early detection is crucial for managing its symptoms. We recently developed a method for calculating pulmonary blood mass change (PBMC) apparent on paired inhale/exhale non-contrast computed tomography (CT) scans as a quantitative surrogate for lung perfusion. Our long term objective is to develop a PBMC biomarker for predicting COPD progression. As a first step, we hypothesize that PBMC is significantly lower for non-COPD smokers versus non-COPD non-smokers. Methods: CT scans from 77 healthy …

Predicting Benefit From Immune Checkpoint Inhibitors In Patients With Non-Small-Cell Lung Cancer By Ct-Based Ensemble Deep Learning: A Retrospective Study, Maliazurina B Saad, Lingzhi Hong, Muhammad Aminu, Natalie I Vokes, Pingjun Chen, Morteza Salehjahromi, Kang Qin, Sheeba J Sujit, Xuetao Lu, Elliana Young, Qasem Al-Tashi, Rizwan Qureshi, Carol C Wu, Brett W Carter, Steven H Lin, Percy P Lee, Saumil Gandhi, Joe Y Chang, Ruijiang Li, Michael F Gensheimer, Heather A Wakelee, Joel W Neal, Hyun-Sung Lee, Chao Cheng, Vamsidhar Velcheti, Yanyan Lou, Milena Petranovic, Waree Rinsurongkawong, Xiuning Le, Vadeerat Rinsurongkawong, Amy Spelman, Yasir Y Elamin, Marcelo V Negrao, Ferdinandos Skoulidis, Carl M Gay, Tina Cascone, Mara B Antonoff, Boris Sepesi, Jeff Lewis, Ignacio I Wistuba, John D Hazle, Caroline Chung, David Jaffray, Don L Gibbons, Ara Vaporciyan, J Jack Lee, John V Heymach, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

BACKGROUND: Only around 20-30% of patients with non-small-cell lung cancer (NCSLC) have durable benefit from immune-checkpoint inhibitors. Although tissue-based biomarkers (eg, PD-L1) are limited by suboptimal performance, tissue availability, and tumour heterogeneity, radiographic images might holistically capture the underlying cancer biology. We aimed to investigate the application of deep learning on chest CT scans to derive an imaging signature of response to immune checkpoint inhibitors and evaluate its added value in the clinical context.

METHODS: In this retrospective modelling study, 976 patients with metastatic, EGFR/ALK negative NSCLC treated with immune checkpoint inhibitors at MD Anderson and Stanford were enrolled from …

On The Respiratory Syncytial Virus Vaccine, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

No abstract provided.

The Impact Of The Covid-19 Pandemic On Respiratory Syncytial Virus, Amrit Kahlon, Ravina Ramnani, Kartik Rajpal, Yusra Irshad, Sudeep Chapagain, Arushee Bhatnagar, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Twenty-Year Survival Following Lung Transplantation, John James Miggins, Ross M Reul, Spencer Barrett, Abbas Rana, Ahmed Alnajar, Jordan Dunson, Alexis Shafii, Puneet Garcha, John Goss, Gabriel Loor

Faculty, Staff and Students Publications

BACKGROUND: Lung transplantation median survival has seen improvements due to recognition of short-term survival factors but continues to trail behind other solid organs due to limited understanding of long-term survivorship. Given the creation of the United Network for Organ Sharing (UNOS) database in 1986, it was difficult to accrue data on long-term survivors until recently. This study characterizes factors impacting lung transplant survival beyond 20 years, conditional to 1-year survival.

METHODS: Lung transplant recipients listed in UNOS from 1987 to 2002 who survived to 1 post-transplant year were reviewed. Kaplan-Meier and adjusted Cox regression analyses were performed at 20 and …

High-Resolution Transcriptomic And Epigenetic Profiling Identifies Novel Regulators Of Copd, Uwe Schwartz, Maria Llamazares Prada, Stephanie T Pohl, Mandy Richter, Raluca Tamas, Michael Schuler, Corinna Keller, Vedrana Mijosek, Thomas Muley, Marc A Schneider, Karsten Quast, Joschka Hey, Claus P Heußel, Arne Warth, Hauke Winter, Özdemirhan Serçin, Harry Karmouty-Quintana, Soma Sk Jyothula, Manish K Patel, Felix Herth, Ina Koch, Giuseppe Petrosino, Alexandru Titimeaua, Balca R Mardin, Dieter Weichenhan, Tomasz P Jurkowski, Charles D Imbusch, Benedikt Brors, Vladimir Benes, Birgit Jung, David Wyatt, Heiko F Stahl, Christoph Plass, Renata Z Jurkowska

Faculty, Staff and Student Publications

Patients with chronic obstructive pulmonary disease (COPD) are still waiting for curative treatments. Considering its environmental cause, we hypothesized that COPD will be associated with altered epigenetic signaling in lung cells. We generated genome-wide DNA methylation maps at single CpG resolution of primary human lung fibroblasts (HLFs) across COPD stages. We show that the epigenetic landscape is changed early in COPD, with DNA methylation changes occurring predominantly in regulatory regions. RNA sequencing of matched fibroblasts demonstrated dysregulation of genes involved in proliferation, DNA repair, and extracellular matrix organization. Data integration identified 110 candidate regulators of disease phenotypes that were linked …

Her3-Targeted Therapeutic Antibodies And Antibody–Drug Conjugates In Non-Small Cell Lung Cancer Refractory To Egfr-Tyrosine Kinase Inhibitors, Margaret E. Larsen, Hui Lyu, Bolin Liu

School of Medicine Faculty Publications

Human epidermal growth factor receptor 3 (HER3) is a unique member of the human epidermal growth factor receptor (HER/EGFR) family, since it has negligible kinase activity. Therefore, HER3 must interact with a kinase-proficient receptor to form a heterodimer, leading to the activation of signaling cascades. Overexpression of HER3 is observed in various human cancers, including non-small cell lung cancer (NSCLC), and correlates with poor clinical outcomes in patients. Studies on the underlying mechanism demonstrate that HER3-initiated signaling promotes tumor metastasis and causes treatment failure in human cancers. Upregulation of HER3 is frequently observed in EGFR-mutant NSCLC treated with EGFR-tyrosine kinase …

Impact Of An Integrated Classifier Using Biomarkers, Clinical And Imaging Factors On Clinical Decisions Making For Lung Nodules, Fayez Kheir, Juan P. Uribe, Juan Cedeno, Gustavo Munera, Harsh Patel, Ramsy Abdelghani, Atul Matta, Sadia Benzaquen, Regina Villalobos, Adnan Majid

Einstein Health Papers

BACKGROUND: An integrated classifier that utilizes plasma proteomic biomarker along with five clinical and imaging factors was previously shown to be potentially useful in lung nodule evaluation. This study evaluated the impact of the integrated proteomic classifier on management decisions in patients with a pretest probability of cancer (pCA) ≤50% in "real-world" clinical setting.

METHODS: Retrospective study examining patients with lung nodules who were evaluated using the integrated classifier as compared to standard clinical care during the same period, with at least 1-year follow-up.

RESULTS: A total of 995 patients were evaluated for lung nodules over 1 year following the …

Bronchopulmonary Dysplasia: Ongoing Challenges From Definitions To Clinical Care, Sushma Nuthakki, Kaashif Ahmad, Gloria Johnson, Milenka Cuevas Guaman

Faculty, Staff and Students Publications

Bronchopulmonary dysplasia (BPD) is the most common complication of extreme prematurity. Its etiology is multifactorial and is attributed to genetic susceptibility to prenatal and postnatal factors. As advancements in neonatology have led to the increased survival of premature infants, a parallel increase in the incidence of BPD has occurred. Over time, the definition and diagnostic criteria for BPD have evolved, as have management strategies. However, challenges continue to exist in the management of these infants, which is not surprising given the complexity of the disease. We summarize the key diagnostic criteria and provide insight into the challenges related to various …

Comparing Pleural Fluid Removal Volume And Oxygenation Change In Therapeutic Thoracentesis: Is There A Relationship?, Hannah Zazulak, Ryanne Burke, Andrea Bodine

Advances in Clinical Medical Research and Healthcare Delivery

Background: During therapeutic thoracentesis (TT), pleural fluid is typically drained to completion. Fluid removal improves oxygenation, and the amount of fluid removed is directly associated with the risk of serious complications. A relationship between the amount of fluid removed during TT and the change in oxygenation has not been found in the literature. A direct relationship was hypothesized in this study. Differences in the change in oxygenation between sexes, age, and pre-procedure oxygen support were secondarily hypothesized. This information would assist in the guidance of future TT protocols.

Methods: Subjects of this retrospective cohort study were males and females aged …

Extrinsic Allergic Alveolitis: A Systematic Review Of Hla-Dr In Pigeon Breeder’S Disease, Dylan Thibaut, Ryan A. Witcher, Anitha Kunnath, James Toldi

Advances in Clinical Medical Research and Healthcare Delivery

Abstract

Introduction: Pigeon Breeder’s Pneumonitis (PBP) results due to a complex pathophysiology that includes exposure to avian antigens. Susceptibility has been linked to human leukocyte antigen (HLA) class II, though consensus has not been reached. The goal of this systematic review is to further elucidate the association between PBP and HLA-DR subtypes.

Methods: Databases utilized included PubMed, Google Scholar, ScienceDirect, and Cochrane Library. Inclusion required a minimum of three studies in English presenting HLA-DR alleles of PBP and control subgroups. Exclusion was due to insufficient data or non-feasible control groups. Forest plots were created for HLA-DR subtypes’ association …

Prognostic Value Of Severe Acute Respiratory Syndrome Coronavirus-2 Viral Load And Antibodies In Patients Hospitalized With Covid-19, Rebecca N Bauer, Anastasia Teterina, Haridha Shivram, Jacqueline Mcbride, Carrie M Rosenberger, Fang Cai, Min Bao, Larry Tsai, Oliver Gordon, Ivan T Lee, Jeffrey J Wallin, Danielle Porter, Kavita Juneja, Gregory Camus, Ivan O Rosas, Steffen Wildum

Faculty, Staff and Students Publications

Observational studies have identified the potential prognostic value for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load and anti-SARS-CoV-2 antibodies in coronavirus disease 2019 (COVID-19). However, viral load in nasopharyngeal (NP) swabs produced inconsistent results in prognostic analyses, and the prognostic value of viral load or antibodies has not been confirmed in large clinical trials. COVACTA and REMDACTA were double-blind, randomized, controlled trials with a combined enrollment of 1078 patients hospitalized with COVID-19 treated with tocilizumab or placebo in COVACTA or tocilizumab plus remdesivir or placebo plus remdesivir in REMDACTA. We assessed the potential prognostic value of NP and serum …

Quantifying Disease Progression In Copd Patients By Forecasting Pft Scores Using Extracted Features From Non-Contrast Ct, A T. Luong, C J. Herrera, E Young, Y K. Liu, A Nowacki, J Cisneros-Paz, Girish Nair, E Castillo

Conference Presentation Abstracts

Purpose: Currently there is no validated method for quantifying risk of disease progression in chronic obstructive pulmonary disease (COPD). We aim to address this by predicting whether a patient will worsen using a machine learning model trained on basic patient information, current pulmonary function values, FEV1 and FVC, and extracted features from a non-contrast CT scan. Disease severity is characterized by these pulmonary function values, and by extension disease progression can be determined by the change in these values between future timepoints. Methods: XGBoost, a popular classification library that utilizes gradient boosted trees, was used to define an ensemble model …

Quantifying Disease Progression In Copd Patients By Forecasting Pft Scores Using Extracted Features From Non-Contrast Ct, A T. Luong, C J. Herrera, E Young, Y K. Liu, A Nowacki, J Cisneros-Paz, Girish Nair, E Castillo

Conference Presentation Abstracts

Purpose: Currently there is no validated method for quantifying risk of disease progression in chronic obstructive pulmonary disease (COPD). We aim to address this by predicting whether a patient will worsen using a machine learning model trained on basic patient information, current pulmonary function values, FEV1 and FVC, and extracted features from a non-contrast CT scan. Disease severity is characterized by these pulmonary function values, and by extension disease progression can be determined by the change in these values between future timepoints. Methods: XGBoost, a popular classification library that utilizes gradient boosted trees, was used to define an ensemble model …

A Nasal Inflammatory Cytokine Signature Is Associated With Early Graft-Versus-Host Disease Of The Lung After Allogeneic Hematopoietic Cell Transplantation: Proof Of Concept, Edwin J Ostrin, Nicholas L Rider, Amin M Alousi, Ehsan Irajizad, Liang Li, Qian Peng, Sang T Kim, Lara Bashoura, Muhammad H Arain, Laila Z Noor, Nikul Patel, Rohtesh Mehta, Uday R Popat, Chitra Hosing, Robert R Jenq, Gabriela Rondon, Samir M Hanash, Sophie Paczesny, Elizabeth J Shpall, Richard E Champlin, Burton F Dickey, Ajay Sheshadri

Faculty, Staff and Student Publications

Respiratory inflammation in bronchiolitis obliterans syndrome (BOS) after hematopoietic cell transplantation (HCT) is poorly understood. Clinical criteria for early-stage BOS (stage 0p) often capture HCT recipients without BOS. Measuring respiratory tract inflammation may help identify BOS, particularly early BOS. We conducted a prospective observational study in HCT recipients with new-onset BOS (n = 14), BOS stage 0p (n = 10), and recipients without lung impairment with (n = 3) or without (n = 8) chronic graft-versus-host disease and measured nasal inflammation using nasosorption at enrollment and then every 3 mo for 1 y. We divided BOS stage 0p into impairment …

Redox-Dependent Activation Of Lung Epithelial Stat3 Is Required For Inducible Protection Against Bacterial Pneumonia, Vikram V Kulkarni, Yongxing Wang, Jezreel Pantaleon Garcia, Scott E Evans

Faculty, Staff and Student Publications

The lung epithelium is dynamic, capable of considerable structural and functional plasticity in response to pathogen challenges. Our laboratory has demonstrated that an inhaled combination of a Toll-like receptor (TLR) 2/6 agonist and a TLR9 agonist (Pam2ODN) results in robust protection against otherwise lethal pneumonias. We have previously shown that intact epithelial TLR signaling and generation of multisource epithelial reactive oxygen species (ROS) are required for inducible protection. Further investigating the mechanisms underlying this phenomenon of inducible resistance, reverse-phase protein array analysis demonstrated robust STAT3 (signal transducer and activator of transcription 3) phosphorylation following treatment of lung epithelial cells. We …

Genome-Wide Association Study Of Lung Adenocarcinoma In East Asia And Comparison With A European Population, Jianxin Shi, Kouya Shiraishi, Jiyeon Choi, Keitaro Matsuo, Tzu-Yu Chen, Juncheng Dai, Rayjean J Hung, Kexin Chen, Xiao-Ou Shu, Young Tae Kim, Maria Teresa Landi, Dongxin Lin, Wei Zheng, Zhihua Yin, Baosen Zhou, Bao Song, Jiucun Wang, Wei Jie Seow, Lei Song, I-Shou Chang, Wei Hu, Li-Hsin Chien, Qiuyin Cai, Yun-Chul Hong, Hee Nam Kim, Yi-Long Wu, Maria Pik Wong, Brian Douglas Richardson, Karen M Funderburk, Shilan Li, Tongwu Zhang, Charles Breeze, Zhaoming Wang, Batel Blechter, Bryan A Bassig, Jin Hee Kim, Demetrius Albanes, Jason Y Y Wong, Min-Ho Shin, Lap Ping Chung, Yang Yang, She-Juan An, Hong Zheng, Yasushi Yatabe, Xu-Chao Zhang, Young-Chul Kim, Neil E Caporaso, Jiang Chang, James Chung Man Ho, Michiaki Kubo, Yataro Daigo, Minsun Song, Yukihide Momozawa, Yoichiro Kamatani, Masashi Kobayashi, Kenichi Okubo, Takayuki Honda, Dean H Hosgood, Hideo Kunitoh, Harsh Patel, Shun-Ichi Watanabe, Yohei Miyagi, Haruhiko Nakayama, Shingo Matsumoto, Hidehito Horinouchi, Masahiro Tsuboi, Ryuji Hamamoto, Koichi Goto, Yuichiro Ohe, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Megumi Hara, Yuichiro Nishida, Kenji Takeuchi, Kenji Wakai, Koichi Matsuda, Yoshinori Murakami, Kimihiro Shimizu, Hiroyuki Suzuki, Motonobu Saito, Yoichi Ohtaki, Kazumi Tanaka, Tangchun Wu, Fusheng Wei, Hongji Dai, Mitchell J Machiela, Jian Su, Yeul Hong Kim, In-Jae Oh, Victor Ho Fun Lee, Gee-Chen Chang, Ying-Huang Tsai, Kuan-Yu Chen, Ming-Shyan Huang, Wu-Chou Su, Yuh-Min Chen, Adeline Seow, Jae Yong Park, Sun-Seog Kweon, Kun-Chieh Chen, Yu-Tang Gao, Biyun Qian, Chen Wu, Daru Lu, Jianjun Liu, Ann G Schwartz, Richard Houlston, Margaret R Spitz, Ivan P Gorlov, Xifeng Wu, Ping Yang, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, Bu-Tian Ji, H-Erich Wichmann, David C Christiani, Gadi Rennert, Susanne Arnold, Paul Brennan, James Mckay, John K Field, Sanjay S Shete, Loic Le Marchand, Geoffrey Liu, Angeline Andrew, Lambertus A Kiemeney, Shan Zienolddiny-Narui, Kjell Grankvist, Mikael Johansson, Angela Cox, Fiona Taylor, Jian-Min Yuan, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Hyo-Sung Jeon, Shih Sheng Jiang, Jae Sook Sung, Chung-Hsing Chen, Chin-Fu Hsiao, Yoo Jin Jung, Huan Guo, Zhibin Hu, Laurie Burdett, Meredith Yeager, Amy Hutchinson, Belynda Hicks, Jia Liu, Bin Zhu, Sonja I Berndt, Wei Wu, Junwen Wang, Yuqing Li, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Li Liu, Chang Hyun Kang, Wen-Chang Wang, Jun Xu, Peng Guan, Wen Tan, Chong-Jen Yu, Gong Yang, Alan Dart Loon Sihoe, Ying Chen, Yi Young Choi, Jun Suk Kim, Ho-Il Yoon, In Kyu Park, Ping Xu, Qincheng He, Chih-Liang Wang, Hsiao-Han Hung, Roel C H Vermeulen, Iona Cheng, Junjie Wu, Wei-Yen Lim, Fang-Yu Tsai, John K C Chan, Jihua Li, Hongyan Chen, Hsien-Chih Lin, Li Jin, Jie Liu, Norie Sawada, Taiki Yamaji, Kathleen Wyatt, Shengchao A Li, Hongxia Ma, Meng Zhu, Zhehai Wang, Sensen Cheng, Xuelian Li, Yangwu Ren, Ann Chao, Motoki Iwasaki, Junjie Zhu, Gening Jiang, Ke Fei, Guoping Wu, Chih-Yi Chen, Chien-Jen Chen, Pan-Chyr Yang, Jinming Yu, Victoria L Stevens, Joseph F Fraumeni, Nilanjan Chatterjee, Olga Y Gorlova, Chao Agnes Hsiung, Christopher I Amos, Hongbing Shen, Stephen J Chanock, Nathaniel Rothman, Takashi Kohno, Qing Lan

Faculty, Staff and Student Publications

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European …

Tapped Twice: A Case Of A Rapidly Re-Accumulating Hepatic Hydrothorax In A Patient With Spontaneous Bacterial Empyema, Amir Khalil, Suma Alzouhayli, Silvia Novakova, Saad Shams, Ahmad Baiyasi, Maria Khalil, Mohammed Uddin, Aryan Shiari, Kareem Bazzy

The University of Louisville Journal of Respiratory Infections

Hepatic hydrothorax (HH) is a complication of decompensated liver cirrhosis that only occurs in about 5–6% of cirrhosis patients, defined as a pleural fluid in the setting of known liver disease, with the absence of any other cardiopulmonary etiology. Infected HH is a rare complication, designated as spontaneous bacterial empyema (SBEM), found in only 13–16% of patients with HH. This case follows a patient with SBEM who developed a recurrent pleural effusion minutes after thoracentesis. Our patient is a 56-year-old female with a history of alcoholic cirrhosis with pleuritic pain found to have right-sided pleural effusion with decompensation. She had …

Toll-Like Receptors 2, 4, And 9 Modulate Promoting Effect Of Copd-Like Airway Inflammation On K-Ras-Driven Lung Cancer Through Activation Of The Myd88/Nf-ĸb Pathway In The Airway Epithelium, Walter V Velasco, Nasim Khosravi, Susana Castro-Pando, Nelly Torres-Garza, Maria T Grimaldo, Avantika Krishna, Michael J Clowers, Misha Umer, Sabah Tariq Amir, Diana Del Bosque, Soudabeh Daliri, Maria Miguelina De La Garza, Marco Ramos-Castaneda, Scott E Evans, Seyed Javad Moghaddam

Faculty, Staff and Student Publications

INTRODUCTION: Toll-like receptors (TLRs) are an extensive group of proteins involved in host defense processes that express themselves upon the increased production of endogenous damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) due to the constant contact that airway epithelium may have with pathogenic foreign antigens. We have previously shown that COPD-like airway inflammation induced by exposure to an aerosolized lysate of nontypeable

METHODS: In the present study, we have dissected the role of TLRs in this process by knocking out TLR2, 4, and 9 and analyzing how these deletions affect the promoting effect of COPD-like airway inflammation on …