Pulmonology Commons^™

Integrative Metabolomics And Transcriptomics Analysis Reveals Novel Therapeutic Vulnerabilities In Lung Cancer, Jose Thaiparambil, Jianrong Dong, Sandra L Grimm, Dimuthu Perera, Chandra Shekar R Ambati, Vasanta Putluri, Matthew J Robertson, Tajhal D Patel, Brandon Mistretta, Preethi H Gunaratne, Min P Kim, Jason T Yustein, Nagireddy Putluri, Cristian Coarfa, Randa El-Zein

Faculty, Staff and Students Publications

BACKGROUND: Non-small cell lung cancer (NSCLC) comprises the majority (~85%) of all lung tumors, with lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) being the most frequently diagnosed histological subtypes. Multi-modal omics profiling has been carried out in NSCLC, but no studies have yet reported a unique metabolite-related gene signature and altered metabolic pathways associated with LUAD and LUSC.

METHODS: We integrated transcriptomics and metabolomics to analyze 30 human lung tumors and adjacent noncancerous tissues. Differential co-expression was used to identify modules of metabolites that were altered between normal and tumor.

RESULTS: We identified unique metabolite-related gene signatures specific for …

Clinical Efficacy Among Patients With Chronic Rhinosinusitis With Nasal Polyps And Clinical Features Of Obstructive Lung Disease: Post Hoc Analysis Of The Phase Iii Sinus-24 And Sinus-52 Studies, Jorge F Maspero, Claus Bachert, Fernando J Martinez, Nicola A Hanania, Benjamin Ortiz, Naimish Patel, Leda P Mannent, Amy Praestgaard, Nami Pandit-Abid, Shahid Siddiqui, Megan Hardin

Faculty, Staff and Students Publications

PURPOSE: To provide a descriptive summary of clinical efficacy and health-related quality of life (HRQoL) measures in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and clinical features of obstructive lung disease in the Phase III dupilumab studies SINUS-24 and SINUS-52 (NCT02912468, NCT02898454).

PATIENTS AND METHODS: Patients met a "broad" definition of having clinical features of obstructive lung disease with any of 3 criteria: (i) pre-bronchodilator forced expiratory volume in 1 second (FEV

RESULTS: Across both studies, 131 patients met the "broad" definition, of whom 90 also had asthma, and 115 patients met the "narrow" definition, of whom 74 had …

Lower Respiratory Illnesses In Childhood Are Associated With The Presence Of Air Trapping In Early Adulthood, Francesca Polverino, Debra A Stern, Eric M Snyder, Courtney Wheatley-Guy, Surya P Bhatt, Fernando D Martinez, Stefano Guerra, Wayne J Morgan

Faculty, Staff and Students Publications

Several factors occurring in early life, including lower respiratory tract illnesses (LRIs), are involved in determining lung structure and function in adulthood, but the effects of these factors on lung development remain largely unknown. Hereby, we evaluated the parameters from computed tomography (CT) scans performed at the age of 26 years in 39 subjects from the birth cohort of the Tucson Children's Respiratory Study (TCRS) in order to determine the relationship between early childhood factors and lung structural changes in young adult life. We found that participants with LRIs in childhood had increased air trapping at the age of 26 …

Corrigendum: Alveolar Macrophages In Lung Cancer: Opportunities And Challenges, Cheng-Yen Chang, Dominique Armstrong, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

In the published article, there was an error in the article title. Instead of “Alveolar Macrophages in Lung Cancer: Opportunities Challenges”, it should be “Alveolar Macrophages in Lung Cancer: Opportunities and Challenges”.

The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.

Respiratory Function Changes As Early Signs Of Amyotrophic Lateral Sclerosis, Mario Polverino, Simone Sampaolo, Antonio Capuozzo, Marco Fasolino, Michele Aliberti, Ersilia Satta, Carlo Santoriello, James Peter Orengo, Francesca Polverino

Faculty, Staff and Students Publications

BACKGROUND: The current diagnostic criteria for amyotrophic lateral sclerosis (ALS) may remain unsatisfactory for months or years in the early disease. Pulmonary assessment has never been considered useful in the early diagnosis of ALS, and studies of pulmonary function in this patient category are lacking.

OBJECTIVES: The objective of this study was to assess the pulmonary function in subjects with unspecific symptoms of ALS in whom an ALS diagnosis cannot be reached based on the current available guidelines.

METHODS: We performed pulmonary function tests, arterial gas analysis, maximal inspiratory (MIP) and expiratory (MEP) pressure, and respiratory drive (P0.1) assessment in …

Myeloid-Associated Differentiation Marker Is Associated With Type 2 Asthma And Is Upregulated By Human Rhinovirus Infection, Sasipa Tanyaratsrisakul, Alane Blythe C Dy, Francesca Polverino, Mari Numata, Julie G Ledford

Faculty, Staff and Students Publications

BACKGROUND: Human rhinoviruses are known to predispose infants to asthma development during childhood and are often associated with exacerbations in asthma patients. MYADM epithelial expression has been shown to associate with asthma severity. The goal of this study was to determine if MYADM expression patterns were altered in asthma and/or rhinovirus infection and if increased MYADM expression is associated with increased asthma-associated factors.

METHODS: Utilizing H1HeLa cells and differentiated primary human airway epithelial cells (AECs), we measured the expression of MYADM and inflammatory genes by qRT-PCR in the presence or absence of RV-1B infection or poly I:C treatment and with …

Cc16 Drives Vla-2-Dependent Splunc1 Expression, Natalie Iannuzo, Holly Welfley, Nicholas C Li, Michael D L Johnson, Joselyn Rojas-Quintero, Francesca Polverino, Stefano Guerra, Xingnan Li, Darren A Cusanovich, Paul R Langlais, Julie G Ledford

Faculty, Staff and Students Publications

RATIONALE: CC16 (Club Cell Secretory Protein) is a protein produced by club cells and other non-ciliated epithelial cells within the lungs. CC16 has been shown to protect against the development of obstructive lung diseases and attenuate pulmonary pathogen burden. Despite recent advances in understanding CC16 effects in circulation, the biological mechanisms of CC16 in pulmonary epithelial responses have not been elucidated.

OBJECTIVES: We sought to determine if CC16 deficiency impairs epithelial-driven host responses and identify novel receptors expressed within the pulmonary epithelium through which CC16 imparts activity.

METHODS: We utilized mass spectrometry and quantitative proteomics to investigate how CC16 deficiency …

Association Of School Infrastructure On Health And Achievement Among Children With Asthma, Tianshi David Wu, Sandra Zaeh, Michelle N Eakin, Kirsten Koehler, Meghan F Davis, Chris Wohn, Ike Diibor, Kevin J Psoter, Curt Cronister, Faith Connolly, Marc Stein, Meredith C Mccormack

Faculty, Staff and Students Publications

OBJECTIVE: To determine whether school infrastructure is associated with health and academic outcomes among elementary school children with asthma.

METHODS: We conducted a retrospective cohort study of linked medical, academic, and facilities data from a large mid-Atlantic school district of the United States. All K-5 students with asthma who were enrolled under the state's Children's Health Insurance Program were included. We estimated associations of the infrastructure quality of the student's school, as assessed by an engineering firm in Summer 2011 and represented by the Facility Condition Index (FCI), with asthma health outcomes, absenteeism, and standardized test scores in math and …

Peptidylarginine Deiminase 2 Citrullinates Mzb1 And Promotes The Secretion Of Igm And Iga, Benjamin Geary, Bo Sun, Ronak R Tilvawala, Leonard Barasa, Konstantin Tsoyi, Ivan O Rosas, Paul R Thompson, I-Cheng Ho

Faculty, Staff and Students Publications

INTRODUCTION: MZB1 is an endoplasmic reticulum residential protein preferentially expressed in plasma cells, marginal zone and B1 B cells. Recent studies on murine B cells show that it interacts with the tail piece of IgM and IgA heavy chain and promotes the secretion of these two classes of immunoglobulin. However, its role in primary human B cells has yet to be determined and how its function is regulated is still unknown. The conversion of peptidylarginine to peptidylcitrulline, also known as citrullination, by peptidylarginine deiminases (PADs) can critically influence the function of proteins in immune cells, such as neutrophils and T …

Distinct Temporal Trajectories And Risk Factors For Post-Acute Sequelae Of Sars-Cov-2 Infection, Chen Chen, Sairam Parthasarathy, Jacqueline M Leung, Michelle J Wu, Katherine A Drake, Vanessa K Ridaura, Howard C Zisser, William A Conrad, Victor F Tapson, James N Moy, Christopher R Defilippi, Ivan O Rosas, Bellur S Prabhakar, Mujeeb Basit, Mirella Salvatore, Jerry A Krishnan, Charles C Kim

Faculty, Staff and Students Publications

BACKGROUND: The understanding of Post-acute sequelae of SARS-CoV-2 infection (PASC) can be improved by longitudinal assessment of symptoms encompassing the acute illness period. To gain insight into the various disease trajectories of PASC, we assessed symptom evolution and clinical factors associated with the development of PASC over 3 months, starting with the acute illness period.

METHODS: We conducted a prospective cohort study to identify parameters associated with PASC. We performed cluster and case control analyses of clinical data, including symptomatology collected over 3 months following infection.

RESULTS: We identified three phenotypic clusters associated with PASC that could be characterized as …

Lymphangioleiomyomatosis: Circulating Levels Of Fgf23 And Pulmonary Diffusion, Anthony J Esposito, Jewel Imani, Shikshya Shrestha, Shefali Bagwe, Anthony M Lamattina, Marina Vivero, Hilary J Goldberg, Ivan O Rosas, Elizabeth P Henske, Souheil Y El-Chemaly

Faculty, Staff and Students Publications

OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare, destructive disease of the lungs with a limited number of determinants of disease activity, which are a critical need for clinical trials. FGF23 has been implicated in several chronic pulmonary diseases. We aimed to determine the association between serum FGF23 levels and pulmonary function in a cohort of patients with LAM.

METHODS: This was a descriptive single-center study in which subjects with LAM and controls with unreported lung disease were recruited. Serum FGF23 levels were measured in all subjects. Clinical data, including pulmonary function testing, were retrospectively obtained from electronic medical records of LAM …

Suspected Interstitial Lung Disease In Copdgene Study, Jonathan A Rose, Aravind A Menon, Takuya Hino, Akinori Hata, Mizuki Nishino, David A Lynch, Ivan O Rosas, Souheil El-Chemaly, Benjamin A Raby, Samuel Y Ash, Bina Choi, George R Washko, Edwin K Silverman, Michael H Cho, Hiroto Hatabu, Rachel K Putman, Gary M Hunninghake

Faculty, Staff and Students Publications

Rationale

Although interstitial lung abnormalities (ILA), specific patterns of incidentally-detected abnormal density on computed tomography, have been associated with abnormal lung function and increased mortality, it is unclear if a subset with incidental interstitial lung disease (ILD) accounts for these adverse consequences.

Objectives

To define the prevalence and risk factors of suspected ILD and assess outcomes.

Methods

Suspected ILD was evaluated in the COPDGene (Chronic Obstructive Pulmonary Disease Genetic Epidemiology) study, defined as ILA and at least one additional criterion: definite fibrosis on computed tomography, FVC less than 80% predicted, or DL_CO less than 70% predicted. Multivariable linear, longitudinal, …

A Rare Case Of Isolated Thoracic Al-Amyloidoma Causing Complete Atelectasis Of The Right Lung, Smruti Rath, Nicholas Joseph Dcunha, Neel Bhan, Bettye Cox, Muhammad Adrish

Faculty, Staff and Students Publications

Tumoral amyloidosis, or amyloidoma, is a benign, but rare form of amyloidosis that has been reported with a favorable prognosis following surgical resection in some case reports. We present a case of acute on chronic respiratory failure secondary to extensive growth of a thoracic amyloidoma causing atelectasis of the right lung. Our case patient had greater morbidity due to late presentation and extensive disease at diagnosis, precluding any surgical intervention. Radiation therapy and medical management were unsuccessful in reducing disease burden. Early diagnosis and detection are pivotal to improving survival in patients with isolated thoracic amyloidoma.

Quantitative Interstitial Abnormality Progression And Outcomes In The Genetic Epidemiology Of Copd And Pittsburgh Lung Screening Study Cohorts, Bina Choi, Najma Adan, Tracy J Doyle, Ruben San José Estépar, Rola Harmouche, Stephen M Humphries, Matthew Moll, Michael H Cho, Rachel K Putman, Gary M Hunninghake, Ravi Kalhan, Gabrielle Y Liu, Alejandro A Diaz, Stefanie E Mason, Farbod N Rahaghi, Carrie L Pistenmaa, Nicholas Enzer, Clare Poynton, Gonzalo Vegas Sánchez-Ferrero, James C Ross, David A Lynch, Fernando J Martinez, Meilan K Han, Russell P Bowler, David O Wilson, Ivan O Rosas, George R Washko, Raúl San José Estépar, Samuel Y Ash, Copdgene Study And Pittsburgh Lung Screening Study Investigators

Faculty, Staff and Students Publications

BACKGROUND: The risk factors and clinical outcomes of quantitative interstitial abnormality progression over time have not been characterized.

RESEARCH QUESTIONS: What are the associations of quantitative interstitial abnormality progression with lung function, exercise capacity, and mortality? What are the demographic and genetic risk factors for quantitative interstitial abnormality progression?

STUDY DESIGN AND METHODS: Quantitative interstitial abnormality progression between visits 1 and 2 was assessed from 4,635 participants in the Genetic Epidemiology of COPD (COPDGene) cohort and 1,307 participants in the Pittsburgh Lung Screening Study (PLuSS) cohort. We used multivariable linear regression to determine the risk factors for progression and the …

Trib3 Mediates Fibroblast Activation And Fibrosis Though Interaction With Atf4 In Ipf, Lan Wang, Wenyu Zhao, Cong Xia, Zhongzheng Li, Weiming Zhao, Kai Xu, Ningdan Wang, Hui Lian, Ivan O Rosas, Guoying Yu

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by fibroblast activation, excessive deposition of extracellular matrix, and progressive scarring; the pathogenesis remains elusive. The present study explored the role of Tribbles pseudokinase 3 (TRIB3), a well-known stress and metabolic sensor, in IPF. TRIB3 is down-regulated in the lungs of IPF patients in comparison to control subjects. Deficiency of TRIB3 markedly inhibited A549 epithelial cells’ proliferation and migration, significantly reducing wound healing. Conversely, overexpression of TRIB3 promoted A549 cell proliferation and transmigration while it inhibited its apoptosis. Meanwhile, overexpressed TRIB3 inhibited fibroblast activation and decreased ECM …

A Narrative Review Of Sex And Gender Differences In Sleep Disordered Breathing: Gaps And Opportunities, Margaret Bublitz, Nour Adra, Leen Hijazi, Fidaa Shaib, Hrayr Attarian, Ghada Bourjeily

Faculty, Staff and Students Publications

Introduction: Sleep disordered breathing (SDB) is a common condition, associated with multiple comorbidities including cardiovascular and metabolic disease. It has been previously established that SDB is more prevalent in men than women, shifting the literature's focus away from the latter population. As such, underdiagnosis, and thus undertreatment, of SDB in women exists.

Methods: To establish the differences in prevalence, clinical presentation, and pathophysiology of SDB between the two sexes, a narrative review of the current literature was performed.

Results: Rates of SDB are higher among men, likely driven by differences in symptom presentation between men and women, with women presenting …

Understanding Post-Covid-19 Interstitial Lung Disease (Ild): A New Fibroinflammatory Disease Entity, Puja Mehta, Ivan O Rosas, Mervyn Singer

Faculty, Staff and Students Publications

Immunomodulation and immunity from vaccination and natural infection have reduced mortality from coronavirus disease 2019 (COVID-19). However, there are ongoing concerns regarding emerging variants and residual pulmonary sequelae in survivors, given that the lungs are the principal site for the triumvirate of infection, inflammation and injury. The initial waves of acute, severe COVID-19 were profoundly inflammatory, usually manifest as organising pneumonia ± acute respiratory distress syndrome (ARDS). The extent of the fibrogenic potential of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the modifiability of the pathogenic processes and disease course are unclear. Interestingly patients can develop ‘post-COVID interstitial lung disease’ …

Development Of A Novel Mouse Model Of Menopause-Associated Asthma, William P Pederson, Laurie M Ellerman, Estevan C Sandoval, Scott Boitano, Jennifer B Frye, Kristian P Doyle, Heddwen L Brooks, Francesca Polverino, Julie G Ledford

Faculty, Staff and Students Publications

No abstract provided.

Choosing And Switching Biological Agents In Severe Asthma, Muhammad Adrish, Nicola A Hanania

Faculty, Staff and Students Publications

No abstract provided.

Use Of Point-Of-Care Ultrasound And Focus-Assessed Transthoracic Echocardiography To Diagnose Acute Right Heart Failure Due To Fat Emboli In A Parturient, Stephanie O Ibekwe, Varun Potluri, Raja Palvadi, Gavin T Best

Faculty, Staff and Students Publications

Fat embolism syndrome (FES), causing right heart dysfunction, is a rare disease that is often difficult to diagnose with imaging modalities such as computed tomography (CT). FES is the clinical presentation that follows the entry of fat globules into the systemic circulation, which typically results in respiratory failure, scattered petechiae, cardiovascular collapse, and neurological sequelae. It is mostly observed in the cases of orthopedic trauma but may occur in any circumstance where fat can enter the circulatory system. In this case report, the authors describe an atypical presentation of FES in a 24-week parturient. The use of bedside point-of-care ultrasonography …

Chronic Lung Allograft Dysfunction, Anupam Kumar, Puneet Singh Garcha

Faculty, Staff and Students Publications

Lung transplantation remains the only cure for selected patients with advanced irreversible lung diseases. More than 4000 lung transplants are performed worldwide annually. In the last two decades, significant advances have been made in this arena, the most impactful being a modest but improved survival of the recipients. Unfortunately majority of recipients still succumb to chronic lung allograft dysfunction (CLAD), and it remains the most common cause of death after the first year of transplantation. Below is a concise review of the current definition of CLAD, including the various phenotypes, and a brief discussion of the tools available for its …

Obesity And Asthma: A Focused Review, Rubabin Tooba, Tianshi David Wu

Faculty, Staff and Students Publications

No abstract provided.

Characterization And Outcomes Of Hospitalized Children With Coronavirus Disease 2019: A Report From A Multicenter, Viral Infection And Respiratory Illness Universal Study (Coronavirus Disease 2019) Registry, Utpal S Bhalala, Katja M Gist, Sandeep Tripathi, Karen Boman, Vishakha K Kumar, Lynn Retford, Kathleen Chiotos, Allison M Blatz, Heda Dapul, Sourabh Verma, Imran A Sayed, Varsha P Gharpure, Erica Bjornstad, Nancy Tofil, Katherine Irby, Ronald C Sanders, Julia A Heneghan, Melissa Thomas, Manoj K Gupta, Franscene E Oulds, Grace M Arteaga, Emily R Levy, Neha Gupta, Margit Kaufman, Amr Abdelaty, Mark Shlomovich, Shivanand S Medar, A M Iqbal O'Meara, Joshua Kuehne, Shina Menon, Paras B Khandhar, Aaron S Miller, Suzanne M Barry, Valerie C Danesh, Ashish K Khanna, Kimberly Zammit, Casey Stulce, Patrick W Mcgonagill, Asher Bercow, Ioana G Amzuta, Sandeep Gupta, Mohammed A Almazyad, Louisdon Pierre, Prithvi Sendi, Sidra Ishaque, Harry L Anderson, Pooja Nawathe, Murtaza Akhter, Patrick G Lyons, Catherine Chen, Allan J Walkey, Azra Bihorac, Imam Wada Bello, Judith Ben Ari, Tanja Kovacevic, Vikas Bansal, John T Brinton, Jerry J Zimmerman, Rahul Kashyap

Faculty, Staff and Students Publications

OBJECTIVES: Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry.

DESIGN: Retrospective study.

SETTING: Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry.

PATIENTS: Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, …

Adult Memory T Cell Responses To The Respiratory Syncytial Virus Fusion Protein During A Single Rsv Season (2018-2019), Brittani N Blunck, Laura S Angelo, David Henke, Vasanthi Avadhanula, Matthew Cusick, Laura Ferlic-Stark, Lynn Zechiedrich, Brian E Gilbert, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory Syncytial Virus (RSV) is ubiquitous and re-infection with both subtypes (RSV/A and RSV/B) is common. The fusion (F) protein of RSV is antigenically conserved, induces neutralizing antibodies, and is a primary target of vaccine development. Insight into the breadth and durability of RSV-specific adaptive immune response, particularly to the F protein, may shed light on susceptibility to re-infection. We prospectively enrolled healthy adult subjects (n = 19) and collected serum and peripheral blood mononuclear cells (PBMCs) during the 2018–2019 RSV season. Previously, we described their RSV-specific antibody responses and identified three distinct antibody kinetic profiles associated with infection …

Dual Orexin Receptor Antagonists For Treatment Of Insomnia: A Systematic Review And Meta-Analysis On Randomized, Double-Blind, Placebo-Controlled Trials Of Suvorexant And Lemborexant, Habibolah Khazaie, Masoud Sadeghi, Sepideh Khazaie, Max Hirshkowitz, Amir Sharafkhaneh

Faculty, Staff and Students Publications

Study objectives: Recent treatment guidelines for chronic insomnia recommend pharmacological and non-pharmacological therapies. One of the contemporary drug options for insomnia includes dual orexin receptor antagonist (DORA), such as suvorexant and lemborexant. We conducted a systematic review and meta-analysis for the treatment of insomnia with suvorexant and lemborexant based on randomized, double-blind, placebo-controlled Trials.

Methods: We conducted a comprehensive search on three databases (PubMed/Medline, Web of Science, and Cochrane Library) till August 14, 2021, without any restrictions to retrieve the relevant articles. The effect sizes were computed presenting the pooled mean difference or risk ratio along with 95% confidence interval …

Transient Ascaris Suum Larval Migration Induces Intractable Chronic Pulmonary Disease And Anemia In Mice, Yifan Wu, Evan Li, Morgan Knight, Grace Adeniyi-Ipadeola, Li-Zhen Song, Alan R Burns, Ana Clara Gazzinelli-Guimaraes, Ricardo Fujiwara, Maria Elena Bottazzi, Jill E Weatherhead

Faculty, Staff and Students Publications

Ascariasis is one of the most common infections in the world and associated with significant global morbidity. Ascaris larval migration through the host's lungs is essential for larval development but leads to an exaggerated type-2 host immune response manifesting clinically as acute allergic airway disease. However, whether Ascaris larval migration can subsequently lead to chronic lung diseases remains unknown. Here, we demonstrate that a single episode of Ascaris larval migration through the host lungs induces a chronic pulmonary syndrome of type-2 inflammatory pathology and emphysema accompanied by pulmonary hemorrhage and chronic anemia in a mouse model. Our results reveal that …

Mortality, Kidney Failure, And Hospitalization Among Medicare Beneficiaries With Ckd And Pulmonary Hypertension, Sankar D Navaneethan, Carl P Walther, L Parker Gregg, Shweta Bansal, Wolfgang C Winkelmayer, Vijay Nambi, Jingbo Niu

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: Pulmonary hypertension (PH) is highly prevalent among patients with chronic kidney disease (CKD) not requiring kidney replacement therapy. We studied the associations of PH with mortality, kidney failure, as well as cardiovascular (CV) and non-CV hospitalization among Medicare beneficiaries with a CKD diagnosis.

STUDY DESIGN: Retrospective, observational study using a matched cohort design.

SETTING & PARTICIPANTS: Patients with PH (based on 2 claims within 2 years) and patients without PH matched on CKD stage from the Medicare 5% CKD sample (1996-2016).

PREDICTOR: Presence of pulmonary hypertension.

OUTCOME: Mortality, kidney failure, and all-cause, CV, and non-CV hospitalization.

ANALYTICAL …

A Narrative Review Of Interstitial Lung Disease In Anti-Synthetase Syndrome: A Clinical Approach, Naina Sawal, Sanjay Mukhopadhyay, Sheetal Rayancha, Alastair Moore, Puneet Garcha, Anupam Kumar, Viren Kaul

Faculty, Staff and Students Publications

Anti-synthetase syndrome (AS) is a rare autoimmune disorder characterized by the presence of aminoacyl-transfer RNA synthetase antibodies in conjunction with clinical features such as interstitial lung disease (ILD), Raynaud's phenomenon, nonerosive arthritis, and myopathy. AS distinguishes itself from other inflammatory myopathies by its significant lung involvement and rapidly progressive interstitial lung disease (AS-ILD), therefore the management of AS-ILD requires careful clinical, serologic and radiologic assessment. Glucocorticoids are considered the mainstay of therapy; however, additional immunosuppressive agents are often required to achieve disease control. Patient prognosis is highly dependent on early diagnosis and symptom recognition as the antibody profile is thought …

Predicting Lymph Node Metastasis In Non-Small Cell Lung Cancer: Prospective External And Temporal Validation Of The Hal And Homer Models, Gabriela Martinez-Zayas, Francisco A Almeida, Lonny Yarmus, Daniel Steinfort, Donald R Lazarus, Michael J Simoff, Timothy Saettele, Septimiu Murgu, Tarek Dammad, D Kevin Duong, Lakshmi Mudambi, Joshua J Filner, Sofia Molina, Carlos Aravena, Jeffrey Thiboutot, Asha Bonney, Adriana M Rueda, Labib G Debiane, D Kyle Hogarth, Harmeet Bedi, Mark Deffebach, Ala-Eddin S Sagar, Joseph Cicenia, Diana H Yu, Avi Cohen, Laura Frye, Horiana B Grosu, Thomas Gildea, David Feller-Kopman, Roberto F Casal, Michael Machuzak, Muhammad H Arain, Sonali Sethi, George A Eapen, Louis Lam, Carlos A Jimenez, Manuel Ribeiro, Laila Z Noor, Atul Mehta, Juhee Song, Humberto Choi, Junsheng Ma, Liang Li, David E Ost

Faculty, Staff and Students Publications

BACKGROUND: Two models, the Help with the Assessment of Adenopathy in Lung cancer (HAL) and Help with Oncologic Mediastinal Evaluation for Radiation (HOMER), were recently developed to estimate the probability of nodal disease in patients with non-small cell lung cancer (NSCLC) as determined by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). The objective of this study was to prospectively externally validate both models at multiple centers.

RESEARCH QUESTION: Are the HAL and HOMER models valid across multiple centers?

STUDY DESIGN AND METHODS: This multicenter prospective observational cohort study enrolled consecutive patients with PET-CT clinical-radiographic stages T1-3, N0-3, M0 NSCLC undergoing EBUS-TBNA staging. …

Cd148 Deficiency In Fibroblasts Promotes The Development Of Pulmonary Fibrosis, Konstantin Tsoyi, Xiaoliang Liang, Giulia De Rossi, Stefan W Ryter, Kevin Xiong, Sarah G Chu, Xiaoli Liu, Bonna Ith, Lindsay J Celada, Freddy Romero, Matthew J Robertson, Anthony J Esposito, Sergio Poli, Souheil El-Chemaly, Mark A Perrella, Yuanyuan Shi, James Whiteford, Ivan O Rosas

Faculty, Staff and Students Publications

Rationale: CD148/PTRJ (receptor-like protein tyrosine phosphatase η) exerts antifibrotic effects in experimental pulmonary fibrosis via interactions with its ligand syndecan-2; however, the role of CD148 in human pulmonary fibrosis remains incompletely characterized.

Objectives: We investigated the role of CD148 in the profibrotic phenotype of fibroblasts in idiopathic pulmonary fibrosis (IPF).

Methods: Conditional CD148 fibroblast-specific knockout mice were generated and exposed to bleomycin and then assessed for pulmonary fibrosis. Lung fibroblasts (mouse lung and human IPF lung), and precision-cut lung slices from human patients with IPF were isolated and subjected to experimental treatments. A CD148-activating 18-aa mimetic peptide (SDC2-pep) derived from …