Pulmonology Commons^™

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 …

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 …

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 …

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 …

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 …

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 …

Clinical Characteristics And Survival Of Pulmonary Arterial Hypertension With Or Without Interstitial Lung Disease In Systemic Sclerosis, Jessica L Fairley, Dylan Hansen, Laura Ross, Susanna Proudman, Joanne Sahhar, Gene-Siew Ngian, Jennifer Walker, Lauren V Host, Kathleen Morrisroe, Diane Apostolopoulous, Nava Ferdowsi, Michelle Wilson, Maryam Tabesh, Wendy Stevens, Mandana Nikpour

Faculty, Staff and Student Publications

Objectives

To describe the clinical phenotype and prognosis of people in the Australian Scleroderma (SSc) Cohort Study with pulmonary arterial hypertension (PAH) with or without interstitial lung disease (ILD).

Methods

Participants meeting ACR/EULAR criteria for SSc were divided into four mutually exclusive groups: those meeting criteria for PAH (PAH-only), ILD (ILD-only), concurrent PAH and ILD (PAH-ILD) or neither PAH nor ILD (SSc-only). Logistic or linear regression analyses were used for associations between clinical features, health-related quality of life (HRQoL) and physical function. Survival analysis was performed using Kaplan–Meier estimates and Cox-regression modelling.

Results

Of 1561 participants, 7% fulfilled criteria for …

A Postmortem Analysis Of Embalmed Lungs, A Human Cadaver Study, Frederick S. Merdian, Matthew Peterman, Odinaka Osigwe, Vikash Patel, Savita Arya

Research Day

OBJECTIVE: The human cadaveric study is vital to fully understanding lung pathologies and the prevalence of potentially cancerous neoplasms upon death in the general population. Developing an accurate knowledge of human respiratory neoplastic pathology is vital in furthering the field of respiratory medicine. This study aims to analyze a cohort of lung sets belonging to human cadavers for visible potentially pathogenic neoplasms and contrast this with epidemiological data available for representative populations.

METHODS: Cadaveric lungs (n= 20 pairs; 38 individual lungs) were isolated, and gross observations were performed of the parietal surface of both lungs. These samples were part of …

Gold 2023 Update: Implications For Clinical Practice, Diana R. Tamondong-Lachica, Neil Skolnik, John R. Hurst, Nathaniel Marchetti, Adrian Paul J. Rabe, Maria Montes De Oca, Bartolome R. Celli

Abington Jefferson Health Papers

In 2022, over 3 million people died of chronic obstructive pulmonary disease (COPD) and the global burden of the disease is expected to increase over the coming decades. Recommendations for the treatment and management of patients with COPD are published by the Global Initiative for Chronic Obstructive Lung Disease, and updated annually with scientific evidence-based recommendations. The 2023 updates, published in November 2022, contain key changes to recommendations for diagnosis and treatment of COPD that are anticipated to have a significant impact on clinical practice for patients with COPD. Updates to how COPD is defined and diagnosed, including the expansion …

Case Report: Cavitary Pneumonia In A 28 Year Old Male, Dan Zaayenga, Katelyn Courtney

Rowan-Virtua Research Day

Cavitary pneumonia can be caused by several different mechanisms. Such causes include suppurative necrosis (pyogenic lung abscess), caseous necrosis (tuberculosis), ischemic necrosis (pulmonary infarction) cystic dilatation of lung structures (ball value obstruction and Pneumocystis pneumonia) as well as malignant processes. Causes are subject to both environmental factors and host susceptibility. The most common cause of infectious process is tuberculosis with its propensity to cause extensive caseous necrosis. The potential for secondary infection after an individual develops a cavitary pneumonia is also great as it provides a shelter for various pathogens the flourish in an environment otherwise usually well-guarded by host …

Systemic Sclerosis Associated Interstitial Lung Disease: A Conceptual Framework For Subclinical, Clinical And Progressive Disease, David Roofeh, Kevin K Brown, Ella A Kazerooni, Donald Tashkin, Shervin Assassi, Fernando Martinez, Athol U Wells, Ganesh Raghu, Christopher P Denton, Lorinda Chung, Anna-Maria Hoffmann-Vold, Oliver Distler, Kerri A Johannson, Yannick Allanore, Eric L Matteson, Leticia Kawano-Dourado, John D Pauling, James R Seibold, Elizabeth R Volkmann, Simon L F Walsh, Chester V Oddis, Eric S White, Shaney L Barratt, Elana J Bernstein, Robyn T Domsic, Paul F Dellaripa, Richard Conway, Ivan Rosas, Nitin Bhatt, Vivien Hsu, Francesca Ingegnoli, Bashar Kahaleh, Puneet Garcha, Nishant Gupta, Surabhi Khanna, Peter Korsten, Celia Lin, Stephen C Mathai, Vibeke Strand, Tracy J Doyle, Virginia Steen, Donald F Zoz, Juan Ovalles-Bonilla, Ignasi Rodriguez-Pinto, Padmanabha D Shenoy, Andrew Lewandoski, Elizabeth Belloli, Alain Lescoat, Vivek Nagaraja, Wen Ye, Suiyuan Huang, Toby Maher, Dinesh Khanna

Faculty, Staff and Students Publications

OBJECTIVES: To establish a framework by which experts define disease subsets in systemic sclerosis associated interstitial lung disease (SSc-ILD).

METHODS: A conceptual framework for subclinical, clinical and progressive ILD was provided to 83 experts, asking them to use the framework and classify actual SSc-ILD patients. Each patient profile was designed to be classified by at least four experts in terms of severity and risk of progression at baseline; progression was based on 1-year follow-up data. A consensus was reached if ≥75% of experts agreed. Experts provided information on which items were important in determining classification.

RESULTS: Forty-four experts (53%) completed …

Evaluating The Accuracy And Quality Of The Information On Pulmonary Rehabilitation Videos Shared On Youtube Amidst The Covid-19 Pandemic, Payaum Fotovat-Ahmadi, Bilal M. Ali, Bhavinkumar Dalal

Posters

YouTube is a visual library that is growing at incredible pace, especially with the rise of COVID-19 pandemic. Pulmonary rehabilitation refers to the rehabilitation treatment of patients with chronic pulmonary diseases. YouTube has made it possible to practice remote rehabilitation, the effectiveness of which have been proven non-inferior to traditional approaches.

Food Insecurity Screening In People With Cystic Fibrosis, Rebecca Edwards, Lauren Tate, Ana Cairns, Cheryl Coyne, Kathleen Walker, Kim Violette, Ann Ladner, Jessica D'Amico

Costas T. Lambrew Research Retreat 2023

Background: Adequate nutrition is a cornerstone in the management of cystic fibrosis (CF). Malabsorption secondary to pancreatic insufficiency and increased energy demands related to lung disease can increase energy requirements over twofold for a person with CF. Food insecurity (FI) affects approximately 10% of Mainers (1). Per the Cystic Fibrosis Foundation, there may be up to a threefold increase in the prevalence of FI in the CF population (2). To address this issue, we implemented FI screening in the adult and pediatric CF programs to identify the prevalence of FI within our population and to offer immediate interventions.

Access To Pediatric Type 1 Diabetes Care In Montana, James C. Bohnhoff, Michael Kohut Phd, Chelsea Bodnar, Elizabeth A. Jacobs

Costas T. Lambrew Research Retreat 2023

Introduction: Management of Type 1 Diabetes (T1D) requires significant family effort and specialty support. We aimed to understand how living in a rural state impacts families’ experiences during and after diagnosis.

Identification Of Molecular Markers Associated With Copd In Non-Smokers And Smokers: A Bioinformatics Analysis, Agede O. Ayodele, Isa M. Wasagu, Ademola E. Fawibe, Alakija K. Salami

The University of Louisville Journal of Respiratory Infections

Background

Even though the proportional burden of COPD among never-smokers is significant in both developing and developed nations, accounting for around 30% of all COPD in the community, there is little awareness of the prevalence of COPD in this population. Understanding the molecular processes that underlie COPD in nonsmokers is essential.

Methods

Dataset (GSE146560) was acquired from the Gene Expression Omnibus (GEO). The limma and clusterProfiler software tools were used to identify differentially expressed genes (DEGs) and conduct a functional enrichment analysis respectively.

Results

In all, 10,583 DEGs were found, of which 1,065 were up-regulated and 9,518 were down-regulated. The …

Impact Of Structured Reporting Template On The Quality Of Hrct Radiology Reports For Interstitial Lung Disease, Han G. Ngo, Girish B. Nair, Sayf Al-Katib

Posters

This QI study compared the completeness of HRCT radiology reports before and after the implementation of a disease-specific structured reporting template for suspected cases of interstitial lung disease (ILD).

Evaluation Of Phenobarbital In The Treatment Of Alcohol Withdrawal In The Intensive Care Unit, Sienna J. Ringgenberg, Vishal K. Patel

Posters

Alcohol withdrawal syndrome (AWS) is typically managed using the Clinical Institute Withdrawal Assessment (CIWA) protocol which includes benzodiazepines, supportive care, and close clinical monitoring. Alternatives to benzodiazepines such as phenobarbital provide several advantages including less frequent dosing, longer tapering off of doses, and additional glutamate inhibition. The purpose of this study is to evaluate the effectiveness and potential benefit to using phenobarbital in addition to CIWA protocol in the treatment of AWS at Beaumont, Royal Oak.

Defining The Genetic Landscape Of Idiopathic Pulmonary Fibrosis: Role Of Common And Rare Variants, Benjamin J Moss, Ivan O Rosas

Faculty, Staff and Students Publications

No abstract provided.

Genetic Susceptibility To Chronic Obstructive Pulmonary Disease And Idiopathic Pulmonary Fibrosis: The Missing Link?, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

Obstructive Sleep Apnea Modulates Clinical Outcomes Post-Acute Myocardial Infarction: A Large Longitudinal Veterans’ Dataset Report, Ritwick Agrawal, Amir Sharafkhaneh, Vijay Nambi, Ahmed Bahammam, Javad Razjouyan

Faculty, Staff and Students Publications

BACKGROUND: While the longer-term Obstructive Sleep apnea (OSA)-related intermittent hypoxia (IH) leads to various comorbidities, it has become increasingly evident that OSA confers protective advantages during and after acute myocardial infarction (AMI). We hypothesized in patients who were admitted with acute MI, the presence of OSA is associated with lower in-hospital mortality compared to those without a prior diagnosis of OSA.

METHODS: In this nationwide retrospective study utilizing Veterans Health Administration records, we included patients hospitalized for MI with a history of sleep disorders from 1999 to 2020. We divided patients into two cohorts: those with OSA and those without …

Cloning A Profibrotic Stem Cell Variant In Idiopathic Pulmonary Fibrosis, Shan Wang, Wei Rao, Ashley Hoffman, Jennifer Lin, Justin Li, Tao Lin, Audrey-Ann Liew, Matthew Vincent, Tinne C J Mertens, Harry Karmouty-Quintana, Christopher P Crum, Mark L Metersky, David A Schwartz, Peter J A Davies, Clifford Stephan, Soma S K Jyothula, Ajay Sheshadri, Erik Eddie Suarez, Howard J Huang, John F Engelhardt, Burton F Dickey, Kalpaj R Parekh, Frank D Mckeon, Wa Xian

Faculty, Staff and Student Publications

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, and rapidly fatal interstitial lung disease marked by the replacement of lung alveoli with dense fibrotic matrices. Although the mechanisms initiating IPF remain unclear, rare and common alleles of genes expressed in lung epithelia, combined with aging, contribute to the risk for this condition. Consistently, single-cell RNA sequencing (scRNA-seq) studies have identified lung basal cell heterogeneity in IPF that might be pathogenic. We used single-cell cloning technologies to generate "libraries" of basal stem cells from the distal lungs of 16 patients with IPF and 10 controls. We identified a major stem cell …

Immune Cellular Patterns Of Distribution Affect Outcomes Of Patients With Non-Small Cell Lung Cancer, Edwin Roger Parra, Jiexin Zhang, Mei Jiang, Auriole Tamegnon, Renganayaki Krishna Pandurengan, Carmen Behrens, Luisa Solis, Cara Haymaker, John Victor Heymach, Cesar Moran, Jack J Lee, Don Gibbons, Ignacio Ivan Wistuba

Faculty, Staff and Student Publications

Studying the cellular geographic distribution in non-small cell lung cancer is essential to understand the roles of cell populations in this type of tumor. In this study, we characterize the spatial cellular distribution of immune cell populations using 23 makers placed in five multiplex immunofluorescence panels and their associations with clinicopathologic variables and outcomes. Our results demonstrate two cellular distribution patterns-an unmixed pattern mostly related to immunoprotective cells and a mixed pattern mostly related to immunosuppressive cells. Distance analysis shows that T-cells expressing immune checkpoints are closer to malignant cells than other cells. Combining the cellular distribution patterns with cellular …

Nuclear Export Signal Mutation Of Epidermal Growth Factor Receptor Enhances Malignant Phenotypes Of Cancer Cells, Lei Nie, Ying-Nai Wang, Jung-Mao Hsu, Junwei Hou, Yu-Yi Chu, Li-Chuan Chan, Longfei Huo, Yongkun Wei, Rong Deng, Jun Tang, Yi-Hsin Hsu, How-Wen Ko, Seung-Oe Lim, Kebin Huang, Mei-Kuang Chen, Tai-Jan Chiu, Chien-Chia Cheng, Yueh-Fu Fang, Chia-Wei Li, Aarthi Goverdhan, Hsing-Ju Wu, Cheng-Chung Lee, Wen-Ling Wang, Jennifer Hsu, Paul Chiao, Shao-Chun Wang, Mien-Chie Hung

Faculty, Staff and Student Publications

Nuclear epidermal growth factor receptor (EGFR) has been shown to be correlated with drug resistance and a poor prognosis in patients with cancer. Previously, we have identified a tripartite nuclear localization signal (NLS) within EGFR. To comprehensively determine the functions and underlying mechanism of nuclear EGFR and its clinical implications, we aimed to explore the nuclear export signal (NES) sequence of EGFR that is responsible for interacting with the exportins. We combined in silico prediction with site-directed mutagenesis approaches and identified a putative NES motif of EGFR, which is located in amino acid residues 736-749. Mutation at leucine 747 (L747) …

Update On The Role Of Feno In Asthma Management, Neveda Murugesan, Damini Saxena, Arundhati Dileep, Muhammad Adrish, Nicola A Hanania

Faculty, Staff and Students Publications

Asthma is a heterogenous disorder characterized by presence of different phenotypes and endotypes. Up to 10% of the individuals suffer from severe asthma and are at increased risk of morbidity and mortality. Fractional exhaled nitric oxide (FeNO) is a cost-effective, point of care biomarker that is used to detect type 2 airway inflammation. Guidelines have proposed to measure FeNO as an adjunct to diagnostic evaluation in individuals with suspected asthma and to monitor airway inflammation. FeNO has lower sensitivity, suggesting that it may not be a good biomarker to rule out asthma. FeNO may also be used to predict response …

Development Of A Corticosteroid-Immunosuppressed Mouse Model To Study The Pathogenesis And Therapy Of Influenza-Associated Pulmonary Aspergillosis, Sebastian Wurster, Jezreel Pantaleón García, Nathaniel D Albert, Ying Jiang, Keerthi Bhoda, Vikram V Kulkarni, Yongxing Wang, Thomas J Walsh, Scott Evans, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

Influenza-associated pulmonary aspergillosis (IAPA) is a feared complication in patients with influenza tracheobronchitis, especially those receiving corticosteroids. Herein, we established a novel IAPA mouse model with low-inoculum Aspergillus infection and compared outcomes in mice with and without cortisone acetate (CA) immunosuppression. CA was an independent predictor of increased morbidity/mortality in mice with IAPA. Early antifungal treatment with liposomal amphotericin B was pivotal to improve IAPA outcomes in CA-immunosuppressed mice, even after prior antiviral therapy with oseltamivir. In summary, our model recapitulates key clinical features of IAPA and provides a robust preclinical platform to study the pathogenesis and treatment of IAPA.