Pulmonology Commons^™

Combining Clinical And Biological Data To Predict Progressive Pulmonary Fibrosis In Patients With Systemic Sclerosis Despite Immunomodulatory Therapy, Elizabeth R Volkmann, Holly Wilhalme, Shervin Assassi, Grace Hyun J Kim, Jonathan Goldin, Masataka Kuwana, Donald P Tashkin, Michael D Roth

Faculty, Staff and Student Publications

OBJECTIVE: Progressive pulmonary fibrosis (PPF) is the leading cause of death in systemic sclerosis (SSc). This study aimed to develop a clinical prediction nomogram using clinical and biological data to assess risk of PPF among patients receiving treatment of SSc-related interstitial lung disease (SSc-ILD).

METHODS: Patients with SSc-ILD who participated in the Scleroderma Lung Study II (SLS II) were randomized to treatment with either mycophenolate mofetil (MMF) or cyclophosphamide (CYC). Clinical and biological parameters were analyzed using univariable and multivariable logistic regression, and a nomogram was created to assess the risk of PPF and validated by bootstrap resampling.

RESULTS: Among …

Atrial Septal Defect Closure Is Associated With Improved Clinical Status In Patients ≤ 10 Kg With Bronchopulmonary Dysplasia, Melissa K Webb, Milenka Cuevas Guaman, S Kristen Sexson Tejtel, Neil Cambronero, Ryan D Coleman, Corey A Chartan, Betul Yilmaz Furtun, Shaine A Morris, Nidhy P Varghese, Natalie M Villafranco

Faculty, Staff and Students Publications

Patients with bronchopulmonary dysplasia (BPD) have shown clinical improvement after secundum atrial septal defect (ASD) closure. We sought to determine if this post‐ASD closure improvement is secondary to the expected course in BPD patients or related to the closure itself. A novel BPD‐ASD score was created to assess patients' clinical status (higher score = worse disease) and applied to 10 BPD‐ASD inpatients weighing ≤ 10 kg who underwent ASD closure. The score and its subcomponents were retrospectively calculated serially ranging from 8 weeks pre‐ to 8 weeks post‐intervention, and pre‐ and post‐intervention score slopes were created. These slopes were compared …

Bronchopulmonary Dysplasia – Associated Pulmonary Hypertension: An Updated Review, Ahmed El-Saie, Nidhy P Varghese, Melissa K Webb, Natalie Villafranco, Bheru Gandhi, Milenka Cuevas Guaman, Binoy Shivanna

Faculty, Staff and Students Publications

Bronchopulmonary dysplasia (BPD) is the leading cause of chronic lung disease in infants and the commonest complication of prematurity. Advances in respiratory and overall neonatal care have increased the survival of extremely low gestational age newborns, leading to the continued high incidence of BPD. Pulmonary hypertension (PH) represents the severe form of the pulmonary vascular disease associated with BPD, and affects almost one-third of infants with moderate to severe BPD. PH responds suboptimally to pulmonary vasodilators and increases morbidity and mortality in BPD infants. An up-to-date knowledge of the pathogenesis, pathophysiology, diagnosis, treatment, and outcomes of BPD-PH can be helpful …

The Pre-Adaptation Of A Stroke-Specific Self-Management Program Among Older Adults, Timothy Reistetter, Kimberly Hreha, Julianna M Dean, Monique R Pappadis, Rachel R Deer, Chih-Ying Li, Ickpyo Hong, Annalisa Na, Sara Nowakowski, Hashem M Shaltoni, Suresh K Bhavnani

Faculty, Staff and Students Publications

Objectives:

Managing multimorbidity as aging stroke patients is complex; standard self-management programs necessitate adaptations. We used visual analytics to examine complex relationships among aging stroke survivors’ comorbidities. These findings informed pre-adaptation of a component of the Chronic Disease Self-Management Program.

Methods:

Secondary analysis of 2013–2014 Medicare claims with stroke as an index condition, hospital readmission within 90 days (n=42,938), and 72 comorbidities. Visual analytics identified patient subgroups and co-occurring comorbidities. Guided by the framework for reporting adaptations and modifications to evidence-based interventions (FRAME), an interdisciplinary team developed vignettes that highlighted multimorbidity to customize the self-management program.

Results:

There were five …

Obesity Paradox Or Hypoxia Preconditioning: How Obstructive Sleep Apnea Modifies The Obesity-Mi Relationship, Amir Sharafkhaneh, Ritwick Agrawal, Vijay Nambi, Ahmed Bahammam, Javad Razjouyan

Faculty, Staff and Students Publications

OBJECTIVES: The objective of this study was to evaluate the interaction between obesity and obstructive sleep apnea on acute MI in hospital mortality.

METHODS: This retrospective cohort study utilized Veterans Health Administration data from years 1999-2020. Participants were categorized according to their body mass index (BMI) to non-obese (BMI

RESULTS: Among 72,036 veterans with acute-MI hospitalization, individuals with obesity and obstructive sleep apnea (OB-SA) had the lowest in-hospital mortality rate (1.0%) compared to those without obesity and obstructive sleep apnea (nOB-nSA, 2.8%), with obesity but without obstructive sleep apnea (OB-nSA, 2.4%), and with obesity and obstructive sleep apnea (nOB-SA, 1.4%). …

Automated Cellular-Level Dual Global Fusion Of Whole-Slide Imaging For Lung Adenocarcinoma Prognosis, Songhui Diao, Pingjun Chen, Eman Showkatian, Rukhmini Bandyopadhyay, Frank R Rojas, Bo Zhu, Lingzhi Hong, Muhammad Aminu, Maliazurina B Saad, Morteza Salehjahromi, Amgad Muneer, Sheeba J Sujit, Carmen Behrens, Don L Gibbons, John V Heymach, Neda Kalhor, Ignacio I Wistuba, Luisa M Solis Soto, Jianjun Zhang, Wenjian Qin, Jia Wu

Faculty, Staff and Student Publications

Histopathologic whole-slide images (WSI) are generally considered the gold standard for cancer diagnosis and prognosis. Survival prediction based on WSI has recently attracted substantial attention. Nevertheless, it remains a central challenge owing to the inherent difficulties of predicting patient prognosis and effectively extracting informative survival-specific representations from WSI with highly compounded gigapixels. In this study, we present a fully automated cellular-level dual global fusion pipeline for survival prediction. Specifically, the proposed method first describes the composition of different cell populations on WSI. Then, it generates dimension-reduced WSI-embedded maps, allowing for efficient investigation of the tumor microenvironment. In addition, we introduce …

Molecular Insights Using Spatial Transcriptomics Of The Distal Lung In Congenital Diaphragmatic Hernia, Krithika Lingappan, Oluyinka O Olutoye, Abiud Cantu, Manuel Eliezer Cantu Gutierrez, Nahir Cortes-Santiago, J D Hammond, Jamie Gilley, Joselyn Rojas Quintero, Hui Li, Francesca Polverino, Jason P Gleghorn, Sundeep G Keswani

Faculty, Staff and Students Publications

Abnormal pulmonary vascular development and function in congenital diaphragmatic hernia (CDH) is a significant factor leading to pulmonary hypertension. The lung is a very heterogenous organ and has marked cellular diversity that is differentially responsive to injury and therapeutic agents. Spatial transcriptomics provides the unmatched capability of discerning the differences in the transcriptional signature of these distinct cell subpopulations in the lung with regional specificity. We hypothesized that the distal lung parenchyma (selected as a region of interest) would show a distinct transcriptomic profile in the CDH lung compared with control (normal lung). We subjected lung sections obtained from male …

Examination Of Disparities In Prehospital Encounters For Pediatric Asthma Exacerbations, Lauren Riney, Sam Palmer, Erik Finlay, Andrew Bertrand, Shannon Burcham, Phyllis Hendry, Manish Shah, Kathryn Kothari, David W Ashby, Daniel Ostermayer, Olga Semenova, Benjamin N Abo, Benjamin Abes, Nichole Shimko, Emily Myers, Marshall Frank, Tim Turner, Mac Kemp, Kim Landry, Greg Roland, Jennifer N Fishe

Faculty, Staff and Student Publications

INTRODUCTION: There are disparities in multiple aspects of pediatric asthma care; however, prehospital care disparities are largely undescribed. This study's objective was to examine racial and geographic disparities in emergency medical services (EMS) medication administration to pediatric patients with asthma.

METHODS: This is a substudy of the Early Administration of Steroids in the Ambulance Setting: An Observational Design Trial, which includes data from pediatric asthma patients ages 2-18 years. We examined rates of EMS administration of systemic corticosteroids and inhaled bronchodilators by patient race. We geocoded EMS scene addresses, characterized the locations' neighborhood-based conditions and resources relevant to children using …

Cocaine Use Disorder Effects On Blood Oxytocin Levels And Oxtr Dna Methylation, Manassés Soares Souza, Breno Sanvicente-Vieira, Aline Zaparte, Talita Baptista, Maria Aparecida Nagai, Flávia Rotea Mangone, Ana Carolina Pavanelli, Thiago Wendt Viola, Rodrigo Grassi-Oliveira

School of Medicine Faculty Publications

Substance use disorders have been associated with alterations in the oxytocinergic system, but few studies have investigated both the peptide and epigenetic mechanisms potentially implicated in the regulation of oxytocin receptor. In this study, we compared plasma oxytocin and blood DNA methylation in the OXTR gene between people with and without cocaine use disorder (CUD). We measured the oxytocin levels of 51 people with CUD during acute abstinence and of 30 healthy controls using an enzyme immunoassay. The levels of DNA methylation in four CpG sites at exon III of the OXTR gene were evaluated in a subsample using pyrosequencing. …

Heterogenous Lung Inflammation Ct Patterns Distinguish Pneumonia And Immune Checkpoint Inhibitor Pneumonitis And Complement Blood Biomarkers In Acute Myeloid Leukemia: Proof Of Concept, Muhammad Aminu, Naval Daver, Myrna C B Godoy, Girish Shroff, Carol Wu, Luis F Torre-Sada, Alberto Goizueta, Vickie R Shannon, Saadia A Faiz, Mehmet Altan, Guillermo Garcia-Manero, Hagop Kantarjian, Farhad Ravandi-Kashani, Tapan Kadia, Marina Konopleva, Courtney Dinardo, Sherry Pierce, Aung Naing, Sang T Kim, Dimitrios P Kontoyiannis, Fareed Khawaja, Caroline Chung, Jia Wu, Ajay Sheshadri

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICI) may cause pneumonitis, resulting in potentially fatal lung inflammation. However, distinguishing pneumonitis from pneumonia is time-consuming and challenging. To fill this gap, we build an image-based tool, and further evaluate it clinically alongside relevant blood biomarkers.

MATERIALS AND METHODS: We studied CT images from 97 patients with pneumonia and 29 patients with pneumonitis from acute myeloid leukemia treated with ICIs. We developed a CT-derived signature using a habitat imaging algorithm, whereby infected lungs are segregated into clusters ("habitats"). We validated the model and compared it with a clinical-blood model to determine whether imaging can add …

Supradiaphragmatic Origin Of The Celiac Trunk Leading To Median Arcuate Ligament Syndrome With Superior Mesenteric Artery Involvement, Martina Rama, Wissam Nasser, Prashanth Palvannan, Sara Belko, Paul Dimuzio, Francesco Palazzo

Department of Surgery Faculty Papers

Median arcuate ligament (MAL) syndrome (MALS) is a rare condition caused by compression of the celiac artery by the MAL. Symptoms include abdominal pain, nausea, and weight loss. Rarely, the MAL can compress both the celiac artery and the superior mesenteric artery (SMA). We describe the case of a young man with MALS involving the celiac artery and SMA. Laparoscopic release of the MAL was performed, and the patient had resolution of his symptoms at 6 months of follow-up. A review of the literature identified only six cases of MALS involving the SMA and celiac artery, making this a rare …

Role Of A Multidisciplinary Pulmonary Embolism Response Team And Impact Of Interventional Therapy In The Management Of Patients With Intermediate-High Risk Pulmonary Embolism, Juan N Pulido, Robert Fletcher, Michelle A. Poitevin, Kristina Pratt, Paul P Huang, Eric J Lehr, George P Pappas

Articles, Abstracts, and Reports

Background: Despite emerging interventional options for pulmonary embolism (PE), the mortality rate for intermediate high-risk PE (IHR-PE) remains high and the optimal therapeutic approach unclear due to a lack of robust outcomes data. We describe the outcomes of patients presenting with IHR-PE managed by a multidisciplinary PERT program with all available reperfusion options.

Methods: This single center retrospective study included EMR data from patients that were a part of the multidisciplinary PERT program from January 2012 to June 2023. PERT was activated if risk of death was intermediate or higher. The simplified pulmonary embolism severity index (sPESI) and Bova score …

Outcomes Of Patients With Intermediate Risk Pulmonary Embolism Treated With A Multidisciplinary Pulmonary Embolism Response Team. The Emergent Role Of Percutaneous Catheter Thrombectomy And The Importance Of Cardiac Surgery Engagement, Juan N Pulido, Robert Fletcher, Michelle A. Poitevin, Kristina Pratt, Paul P Huang, George P Pappas, Eric J Lehr

Articles, Abstracts, and Reports

Background: Management of Intermediate Risk Pulmonary Embolism (IRPE) remains controversial due to the dynamic nature of the disease and the lack of correlative outcomes with large clot burden. We describe the outcomes of patients presenting with IRPE managed by a multidisciplinary Pulmonary Embolism Response Team (PERT).

Methods: This single center retrospective study included EMR data from patients that were a part of the multidisciplinary PERT program from January 2012 to June 2023. PERT was activated if risk of death was intermediate or higher. The simplified pulmonary embolism severity index (sPESI) and Bova score were used as risk stratification tools. Patients …

Associations Between Telomere Attrition, Genetic Variants In Telomere Maintenance Genes, And Non-Small Cell Lung Cancer Risk In The Jammu And Kashmir Population Of North India, Gh Rasool Bhat, Rajeshwer Singh Jamwal, Itty Sethi, Amrita Bhat, Ruchi Shah, Sonali Verma, Minerva Sharma, Hana Q Sadida, Sara K Al-Marzooqi, Tariq Masoodi, Sameer Mirza, Mohammad Haris, Muzafar A Macha, Ammira S Alshabeeb Akil, Ajaz A Bhat, Rakesh Kumar

Faculty, Staff and Student Publications

BACKGROUND: Telomeres are repetitive DNA sequences located at the ends of chromosomes, playing a vital role in maintaining chromosomal integrity and stability. Dysregulation of telomeres has been implicated in the development of various cancers, including non-small cell lung cancer (NSCLC), which is the most common type of lung cancer. Genetic variations within telomere maintenance genes may influence the risk of developing NSCLC. The present study aimed to evaluate the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India, and to investigate the relationship between telomere length and NSCLC risk.

METHODS: We …

The Philadelphia Lung Cancer Learning Community: A Multi-Health-System, Citywide Approach To Lung Cancer Screening, Julie A. Barta, Cherie P. Erkmen, Christine S. Shusted, Ronald E. Myers, Chelsea Saia, Sarah Cohen, Jocelyn Wainwright, Charnita Zeigler-Johnson, Farouk Dako, Richard Wender, Gregory C. Kane, Anil Vachani, Katharine A. Rendle

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

Background

Lung cancer screening uptake for individuals at high risk is generally low across the United States, and reporting of lung cancer screening practices and outcomes is often limited to single hospitals or institutions. We describe a citywide, multicenter analysis of individuals receiving lung cancer screening integrated with geospatial analyses of neighborhood-level lung cancer risk factors. Methods

The Philadelphia Lung Cancer Learning Community consists of lung cancer screening clinicians and researchers at the 3 largest health systems in the city. This multidisciplinary, multi-institutional team identified a Philadelphia Lung Cancer Learning Community study cohort that included 11 222 Philadelphia residents who …

Transcriptomic And Proteomic Assessment Of Tocilizumab Response In A Randomized Controlled Trial Of Patients Hospitalized With Covid-19, Haridha Shivram, Jason A Hackney, Carrie M Rosenberger, Anastasia Teterina, Aditi Qamra, Olusegun Onabajo, Jacqueline Mcbride, Fang Cai, Min Bao, Larry Tsai, Aviv Regev, Ivan O Rosas, Rebecca N Bauer

Faculty, Staff and Students Publications

High interleukin (IL)-6 levels are associated with greater COVID-19 severity. IL-6 receptor blockade by tocilizumab (anti-IL6R; Actemra) is used globally for the treatment of severe COVID-19, yet a molecular understanding of the therapeutic benefit remains unclear. We characterized the immune profile and identified cellular and molecular pathways modified by tocilizumab in peripheral blood samples from patients enrolled in the COVACTA study, a phase 3, randomized, double-blind, placebo-controlled trial of the efficacy and safety of tocilizumab in hospitalized patients with severe COVID-19. We identified markers of inflammation, lymphopenia, myeloid dysregulation, and organ injury that predict disease severity and clinical outcomes. Proteomic …

Shp2 Promotes Sarcoidosis Severity By Inhibiting Skp2-Targeted Ubiquitination Of Tbet In Cd8+ T Cells, Sherly I Celada, Clarice X Lim, Alexandre F Carisey, Scott A Ochsner, Carlos F Arce Deza, Praveen Rexie, Fernando Poli De Frias, Rafael Cardenas-Castillo, Francesca Polverino, Markus Hengstschläger, Konstantin Tsoyi, Neil J Mckenna, Farrah Kheradmand, Thomas Weichhart, Ivan O Rosas, Luc Van Kaer, Lindsay J Celada

Faculty, Staff and Students Publications

Sarcoidosis is an interstitial lung disease (ILD) characterized by IFNγ and TBET dysregulation. Although one-third of patients progress from granulomatous inflammation to severe lung damage, the molecular mechanisms underlying this process remain unclear. Here, we report that pharmacological inhibition of phosphorylated SH2 containing protein tyrosine phosphatase-2 (pSHP2), a facilitator of aberrant IFNγ levels, decreases large granuloma formation and macrophage infiltration in the lungs of mice with sarcoidosis-like disease. Positive treatment outcomes were dependent on the effective enhancement of TBET ubiquitination within CD8+ T cells. Mechanistically, our findings identified a previously unknown post-translational modification (PTM) pathway in which the E3 F-box …

Pulmonary & Critical Care Insider: Issue 2, Bharat Bajantri Md, Sarah Ellsworth Mls

Critical Care & Pulmonary

Pulmonary & Critical Care Insider Issue 2

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

The goal of this newsletter is to give a brief summary of the most pertinent articles to everyday practice and an attempt to keep up with literature as best as possible. Newsletters go out every 1-2 months.

Summaries/Topics in this issue:

• Spontaneous Breathing Trials
• Enteral feedings
• EFFORT Protein trial
• The NUTRIREA-3 trial
• Veno-venous extracorporeal carbon dioxide removal (vv-ECCO2 R)
• Acute hypoxemic respiratory failure (AHRF)
• Penicillin allergy
• PEN-FAST score
• Etomidate increases mortality …

Design Of A Phase Iii, Double-Blind, Randomised, Placebo-Controlled Trial Of Bi 1015550 In Patients With Progressive Pulmonary Fibrosis (Fibroneer-Ild), Toby M Maher, Shervin Assassi, Arata Azuma, Vincent Cottin, Anna-Maria Hoffmann-Vold, Michael Kreuter, Justin M Oldham, Luca Richeldi, Claudia Valenzuela, Marlies S Wijsenbeek, Carl Coeck, Christina Schlecker, Florian Voss, Daniel Wachtlin, Fernando J Martinez

Faculty, Staff and Student Publications

INTRODUCTION: Progressive pulmonary fibrosis (PPF) includes any diagnosis of progressive fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF). However, disease progression appears comparable between PPF and IPF, suggesting a similar underlying pathology relating to pulmonary fibrosis. Following positive results in a phase II study in IPF, this phase III study will investigate the efficacy and safety of BI 1015550 in patients with PPF (FIBRONEER-ILD).

METHODS AND ANALYSIS: In this phase III, double-blind, placebo-controlled trial, patients are being randomised 1:1:1 to receive BI 1015550 (9 mg or 18 mg) or placebo twice daily over at least 52 weeks, …

Association Between Duration Of Smoking Abstinence Before Non-Small-Cell Lung Cancer Diagnosis And Survival: A Retrospective, Pooled Analysis Of Cohort Studies, Aline F Fares, Yao Li, Mei Jiang, M Catherine Brown, Andrew C L Lam, Reenika Aggarwal, Sabine Schmid, Natasha B Leighl, Frances A Shepherd, Zhichao Wang, Nancy Diao, Angela S Wenzlaff, Juntao Xie, Takashi Kohno, Neil E Caporaso, Curtis Harris, Hongxia Ma, Matthew J Barnett, Leticia Ferro Leal, G Fernandez-Tardon, Mónica Pérez-Ríos, Michael P A Davies, Fiona Taylor, Ben Schöttker, Paul Brennan, David Zaridze, Ivana Holcatova, Jolanta Lissowska, Beata Świątkowska, Dana Mates, Milan Savic, Hermann Brenner, Angeline Andrew, Angela Cox, John K Field, Alberto Ruano-Ravina, Sanjay S Shete, Adonina Tardon, Ying Wang, Loic Le Marchand, Rui Manuel Reis, Matthew B Schabath, Chu Chen, Hongbing Shen, Brid M Ryan, Maria Teresa Landi, Kouya Shiraishi, Jie Zhang, Ann G Schwartz, Ming S Tsao, David C Christiani, Ping Yang, Rayjean J Hung, Wei Xu, Geoffrey Liu

Faculty, Staff and Student Publications

BACKGROUND: The association between duration of smoking abstinence before non-small-cell lung cancer (NSCLC) diagnosis and subsequent survival can influence public health messaging delivered in lung-cancer screening. We aimed to assess whether the duration of smoking abstinence before diagnosis of NSCLC is associated with improved survival.

METHODS: In this retrospective, pooled analysis of cohort studies, we used 26 cohorts participating in Clinical Outcomes Studies of the International Lung Cancer Consortium (COS-ILCCO) at 23 hospitals. 16 (62%) were from North America, six (23%) were from Europe, three (12%) were from Asia, and one (4%) was from South America. Patients enrolled were diagnosed …