Pulmonology Commons^™

Regulation Of Airway Smooth Muscle Cell Proliferation By Diacylglycerol Kinase: Relevance To Airway Remodeling In Asthma, Miguel Angel Hernandez-Lara, Santosh K Yadav, Sushrut D. Shah, Mariko Okumura, Yuichi Yokoyama, Raymond B. Penn,, Taku Kambayashi, Deepak A. Deshpande

Center for Translational Medicine Faculty Papers

Airway remodeling in asthma involves the hyperproliferation of airway smooth muscle (ASM) cells. However, the molecular signals that regulate ASM growth are not completely understood. Gq-coupled G protein-coupled receptor and receptor tyrosine kinase signaling regulate ASM cell proliferation via activation of phospholipase C, generation of inositol triphosphate (IP3) and diacylglycerol (DAG). Diacylglycerol kinase (DGK) converts DAG into phosphatidic acid (PA) and terminates DAG signaling while promoting PA-mediated signaling and function. Herein, we hypothesized that PA is a pro-mitogenic second messenger in ASM, and DGK inhibition reduces the conversion of DAG into PA resulting in inhibition of ASM cell proliferation. We …

Symptom Phenotypes In Pulmonary Arterial Hypertension: The Pah “Symptome”, Lee Ann Matura, Jamison D. Fargo, Kathleen Boyle, Jason S. Fritz, Kerri A. Smith, Jeremy A. Mazurek, Diane Pinder, Christine L. Archer-Chicko, Harold I. Palevsky, Allan I. Pack, Marilyn S. Sommers, Steven M. Kawut

Abington Jefferson Health Papers

Women with pulmonary arterial hypertension (PAH) experience multiple symptoms, including dyspnea, fatigue, and sleep disturbance, that impair their health‐related quality of life (HRQOL). However, we know little about phenotypic subgroups of patients with PAH with similar, concurrent, multiple symptoms. The objectives of this study were to define the “symptome” by symptom cluster phenotypes and compare characteristics such as biomarkers, cardiac structure and function (echocardiography), functional capacity (6‐min walk distance), and HRQOL between the groups. This cross‐sectional study included 60 women with PAH. Subjects completed an assessment battery: Pulmonary Arterial Hypertension Symptom Scale, Pittsburgh Sleep Quality Index, Multidimensional Dyspnea Profile, Patient‐Reported …

Mortality Among Patients With Covid-19 And Different Interstitial Lung Disease Subtypes: A Multicenter Cohort Study., Joy Zhao, Brandon Metra, Gautam George, Jesse Roman, Joseph Mallon, Baskaran Sundaram, Michael Li, Ross Summer

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

No abstract provided.

Racial Difference In Bmi And Lung Cancer Diagnosis: Analysis Of The National Lung Screening Trial, Joy Zhao, Julie Barta, Russell K. Mcintire, Christine S. Shusted, Charnita Zeigler-Johnson, Hee-Soon Juon

Department of Medical Oncology Faculty Papers

Background: The inverse relationship between BMI and lung cancer diagnosis is well defined. However, few studies have examined the racial differences in these relationships. The purpose of this paper is to explore the relationships amongst race, BMI, and lung cancer diagnosis using the National Lung Screening Trial (NLST) data.

Methods: Multivariate regression analysis was used to analyze the BMI, race, and lung cancer diagnosis relationships.

Results: Among 53,452 participants in the NLST cohort, 3.9% were diagnosed with lung cancer, 43% were overweight, and 28% were obese. BMI was inversely related to lung cancer diagnosis among Whites: those overweight (aOR = …

68-Year Old Man With Progressive Weakness And Ventilator Dependent Respiratory Failure: A Case Report Of Sporadic Late Onset Nemaline Myopathy, P. Kirupaharan, Daniel Kramer, Alan Gandler, Lawrence C. Kenyon, Ross Summer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Neuromuscular pathologies must be considered when caring for patients with persistent or progressive respiratory failure. Pertinent disease states may involve skeletal muscles of respiration or associated neurologic structures including motor neurons, peripheral neurons and the neuromuscular junction. Diagnosis may require pulmonary function testing, neurophysiologic studies, imaging, and/or muscle biopsy.

Case presentation: A 68-year-old male was transferred to our intensive care unit (ICU) for management of ventilator dependent respiratory failure. Upon further historical review, he described gradually worsening gait instability and muscle weakness, which was previously attributed to vascular Parkinsonism in the setting of known cerebrovascular disease. Upon arrival to …

Metabolic Syndrome And Acute Respiratory Distress Syndrome In Hospitalized Patients With Covid-19, Joshua L Denson, Aaron S Gillet, Yuanhao Zu, Margo Brown, Thaidan Pham, Yilin Yoshida, Franck Mauvais-Jarvis, Ivor S Douglas, Mathew Moore, Kevin Tea, Andrew Wetherbie, Rachael Stevens, John Lefante, Jeffrey G Shaffer, Donna Lee Armaignac, Katherine Belden, Margit Kaufman, Smith F Heavner, Valerie C Danesh, Sreekanth R Cheruku, Catherine A St Hill, Karen Boman, Neha Deo, Vikas Bansal, Vishakha K Kumar, Allan J Walkey, Rahul Kashyap, Society Of Critical Care Medicine Discovery Viral Infection And Respiratory Illness Universal Study (Virus): Covid-19 Registry Investigator Group

Division of Infectious Diseases and Environmental Medicine Faculty Papers

Importance: Obesity, diabetes, and hypertension are common comorbidities in patients with severe COVID-19, yet little is known about the risk of acute respiratory distress syndrome (ARDS) or death in patients with COVID-19 and metabolic syndrome.

Objective: To determine whether metabolic syndrome is associated with an increased risk of ARDS and death from COVID-19.

Design, setting, and participants: This multicenter cohort study used data from the Society of Critical Care Medicine Discovery Viral Respiratory Illness Universal Study collected from 181 hospitals across 26 countries from February 15, 2020, to February 18, 2021. Outcomes were compared between patients with metabolic syndrome (defined …

Ogr1-Dependent Regulation Of The Allergen-Induced Asthma Phenotype, Ajay P Nayak, Deepak A. Deshpande, Phd, Sushrut D. Shah, Dominic R Villalba, Roslyn Yi, Nadan Wang, Raymond B. Penn

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

The proton-sensing receptor, ovarian cancer G protein-coupled receptor (OGR1), has been shown to be expressed in airway smooth muscle (ASM) cells and is capable of promoting ASM contraction in response to decreased extracellular pH. OGR1 knockout (OGR1KO) mice are reported to be resistant to the asthma features induced by inhaled allergen. We recently described certain benzodiazepines as OGR1 activators capable of mediating both procontractile and prorelaxant signaling in ASM cells. Here we assess the effect of treatment with the benzodiazepines lorazepam or sulazepam on the asthma phenotype in wild-type (WT) and OGR1KO mice subjected to inhaled house dust mite (HDM; …

Association Of Antinuclear Antibody Seropositivity With Inhaled Environmental Exposures In Patients With Interstitial Lung Disease, K. Biblowitz, Cathryn Lee, Daisy Zhu, Imre Noth, Rekha Vij, Mary E Strek, Shashi K Bellam, Ayodeji Adegunsoye

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

Background: Interstitial lung diseases (ILDs) are diffuse parenchymal lung disorders that cause substantial morbidity and mortality. In patients with ILD, elevated antinuclear antibody (ANA) titres may be a sign of an autoimmune process. Inhalational exposures contribute to ILD pathogenesis and affect prognosis and may trigger autoimmune disease. The association of inhalational exposures with ANA seropositivity in ILD patients is unknown.

Methods: This was a retrospective cohort study of adult ILD patients from five centres in the United States. Exposures to tobacco, inhaled organic antigens and inhaled inorganic particles were extracted from medical records. A multivariable logistic regression model was used …

Evaluation Of Asthma Control In Patients With And Without Sinonasal Polyps Following Treatment With Biologic Agents, Prachi Patel, Chandala Chitguppi, Md, Alan Gandler, Md, Kira Murphy, Md, Tawfiq Khoury, Md, Stephanie Bork, Crnp, Pamela Monostra, Pa, Elina Toskala, Md, Phd, Mindy Rabinowitz, Md, Marc Rosen, Md, Gurston Nyquist, Md, Jessica Most, Md

The Medicine Forum

Background: The effects of biologics on severe asthmatics with chronic rhinosinusitis with sinonasal polyposis (CRSwNP) have not been well established. This study evaluates overall control of asthma in patients with and without sinonasal polyps following initiation of biologics therapy.

Methods: Retrospective review of patients with asthma treated with a biologic agent (benralizumab, omalizumab, dupilumab, mepolizumab) and CRSwNP. Charts were assessed for ACT scores at time of biologic enrollment and at 4-7 months.

Results:82 patients met inclusion criteria; 42 (52.5%) patients with asthma and 40 (47.5%) with concurrent sinonasal polyps. The average ACT score for the non-polyp cohort was 13.16 …

Increasing Patient Confidence In Managing Asthma Using Asthma Action Plans, Pankhuri Jha, Jessica F. Most, Md

The Medicine Forum

Asthma is a common illness affecting 8% of the US population and costing $81.9 billion per year.^1,2 Due to its chronic and variable nature, asthmatics need frequent medication adjustments, making management challenging for both physicians and patients. Studies show that patients can control their asthma using an asthma action plan (AAP), which includes directions for daily self-assessment, baseline medications and steps to facilitate detection and treatment of an exacerbation. Self-management education using AAPs is associated with a reduction in hospital admissions and ED visits by 40% and 20%, respectively.³ Despite evidence that AAPs are efficacious, the underlying reason …

Real-World Assessment Of Asthma Specialist Visits Among U.S. Patients With Severe Asthma., Jessica F Most, Christopher S Ambrose, Yen Chung, James L Kreindler, Aimee Near, Stephen Brunton, Yao Cao, Huan Huang, Xiaohui Zhao

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

BACKGROUND: U.S. guidelines recommend that patients with severe asthma be referred to specialists (allergists/immunologists or pulmonologists) for systematic assessment or comanagement; however, contemporary, real-world data on the frequency and impact of specialist care among U.S. severe asthma patients are lacking.

OBJECTIVES: To quantify the frequency of asthma specialist visits among U.S. patients with severe asthma, identify patient demographic and clinical characteristics associated with specialist visits and describe health outcomes following specialist care.

METHODS: Severe asthma patients aged 6 years or older were identified between January 1, 2015, and December 31, 2017, in the IQVIA PharMetrics® Plus database of commercially insured …

Allocation Plans For Crisis Triage: How Well Would They Actually Work?, David Oxman

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

COVID-19 has forced US state governments to create plans for rationing critical care resources that ensure the greatest population benefit. But a study by Jezmir and colleagues in this issue of Cell Reports Medicine raises doubts about whether these plans can distinguish those who would most benefit.

Improving The Use Of Asthma Action Plans, Pooja Pandit, Md, Aaron B. Kaye, Md, Hassan Shahid, Md, Colin Peters, Do, Jessica Most, Md

Health Equity and Quality Improvement (HEQI) Summit

Objectives

• Identify the percentage of asthmatics in Friday fellows’ clinic with an AAP in place.
• Determine if clinician education can increase the number of AAP created for patients.

Quality Of Post-Discharge Follow-Up In Patients Admitted To Tjuh With Intermediate High Risk Pulmonary Embolism, D. Kramer, P. Kirupaharan, M. Flamenbaum, M. Scharf

Health Equity and Quality Improvement (HEQI) Summit

• Our institution has developed a multidisciplinary pulmonary embolism response team (PERT) to help in the management of patients with intermediate high risk pulmonary embolism
• While the PERT focus is on acute inpatient management, it is important that PERT patients have close follow-up to monitor for known future complications including thromboembolic pulmonary hypertension (CTEPH) and chronic pulmonary embolism syndrome
• CTEPH, in particular, is a potentially treatable disease with significant morbidity if left untreated
• Therefore, an underappreciated and important aspect of the PERT team should be the coordinated follow-up and long term care of these patients
• We wanted to better understand how …

Association Of Race With Lung Cancer Risk Among Adults Undergoing Lung Cancer Screening., Christine S Shusted, Nathaniel R Evans, Hee-Soon Juon, Gregory C Kane, Julie A Barta

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

No abstract provided.

Sex Differences In Ischemic Stroke Outcomes In Patients With Pulmonary Hypertension, Tiberiu A Pana, Dana K Dawson, Mohamed O Mohamed, Fiona Murray, David Fischman, Michael Savage, Mamas A Mamas, Phyo K Myint

Division of Cardiology Faculty Papers

BACKGROUND: The association between systemic hypertension and cerebrovascular disease is well documented. However, the impact of pulmonary hypertension (PH) on acute ischemic stroke outcomes is unknown despite PH being recognized as a risk factor for acute ischemic stroke. We aimed to determine the association between PH and adverse in-hospital outcomes after acute ischemic stroke, as well as whether there are sex differences in this association. METHODS AND RESULTS: Acute ischemic stroke admissions from the US National Inpatient Sample between October 2015 and December 2017 were included. The relationship between PH and outcomes (mortality, prolonged hospitalization >4 days, and routine home …

Coronary Vasospasm: Not Gone But Often Forgotten, Michael Savage, Tabitha Moe

Division of Cardiology Faculty Papers

No abstract provided.

A Roller Coaster Ride Of Idiopathic Fibrosing Mediastinitis, Qian Zhang, Khine Shan

Abington Jefferson Health Papers

No abstract provided.

Which Sample Type Is Better For Xpert Mtb/Rif To Diagnose Adult And Pediatric Pulmonary Tuberculosis?, Mengyuan Lyu, Jian Zhou, Yuhui Cheng, Weelic Chong, Kang Wu, Teng Fang, Tianbo Fu, Binwu Ying

Department of Medicine Faculty Papers

OBJECTIVE: This review aimed to identify proper respiratory-related sample types for adult and pediatric pulmonary tuberculosis (PTB), respectively, by comparing performance of Xpert MTB/RIF when using bronchoalveolar lavage (BAL), induced sputum (IS), expectorated sputum (ES), nasopharyngeal aspirates (NPAs), and gastric aspiration (GA) as sample.

METHODS: Articles were searched in Web of Science, PubMed, and Ovid from inception up to 29 June 2020. Pooled sensitivity and specificity were calculated, each with a 95% confidence interval (CI). Quality assessment and heterogeneity evaluation across included studies were performed.

RESULTS: A total of 50 articles were included. The respective sensitivity and specificity were 87% …

Anticoagulation And Bleeding Risk In Patients With Covid-19, Nancy Musoke, Kevin Bryan Lo, Jeri Albano, Eric Peterson, Ruchika Bhargav, Fahad Gul, Robert Dejoy, Grace Salacup, Jerald Pelayo, Padmavathi Tipparaju, Zurab Azmaiparashvili, Gabriel Patarroyo-Aponte, Janani Rangaswami

Department of Medicine Faculty Papers

BACKGROUND: There is no current standardized approach to anticoagulation in patients with Coronavirus Disease 2019 (COVID-19) while potential bleeding risks remain. Our study characterizes the patterns of anticoagulation use in COVID-19 patients and the risk of related bleeding.

METHODS: This is a single center retrospective analysis of 355 adult patients with confirmed diagnosis of COVID-19 from March 1 to May 31, 2020. Chi-square was used to analyze the relationship between degree of anticoagulant dose and bleeding events by site. Multivariable logistic regression was used to look at factors associated with inpatient death.

RESULTS: 61% of patients were being treated with …

Hamman-Rich Syndrome: A Diagnosis Of Exclusion In The Covid-19 Pandemic., Qian Zhang, Ahmad Raza, Vincent Chan, Artem Minalyan, John Madara, Md

Abington Jefferson Health Papers

Hamman-Rich syndrome is a rapidly progressive interstitial lung disease with acute respiratory distress syndrome physiology. It carries a grave prognosis and a high early mortality rate. It is often distinguished from other similar pulmonary pathologies based on the clinical course, laboratory findings, bronchoalveolar lavage testing, and pathology report. We detail a 77-year-old lady with no prior pulmonary disease, smoking history, or occupational and environmental exposures present to the emergency department found to be in acute hypoxic respiratory failure with impressive progressive radiographic findings. The presumptive diagnosis of Hamman-Rich syndrome was made based on a combination of factors after ruling out …

A Silent Fatal Presentation Of Pulmonary Embolism: Reflection And Discussion., Qian Zhang, Zain U. Abideen, Khine S. Shan, Thomas Yoon, Muhammad Farooq

Abington Jefferson Health Papers

Acute pulmonary embolism is a common medical condition that clinicians face in practice. It is important to have a prompt diagnosis with proper management as it is associated with high morbidity and mortality. However, a timely diagnosis is often difficult to obtain especially when the presenting symptoms are atypical, but the consequence could be fatal. We present an 80-year-old gentleman who presented with a near-syncope episode who subsequently was found to have acute extensive bilateral pulmonary embolisms after a code blue event.

A Mysterious Paratracheal Mass: Pulmonary Agenesis., Qian Zhang, Khine S. Shan

Abington Jefferson Health Papers

A 35-year-old lady with a history of possible tuberculosis infection 15 years ago presented to the clinic with the chief complaint of cough. Incidental chest CT showed a right paratracheal and medial right apical heterogeneous soft tissue mass with central areas of calcification that warranted further investigation. A routine endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) discovered isolated lobar pulmonary agenesis as the underlying cause of the mass without findings of malignancy on pathology reports.

Incidental Findings On Ldct For Lung Cancer Screening: Prevalence And Clinical Management, Chris Mcgrath, Md, Mrinalini Venkata-Subramani, Md, Brandon Menachem, Md, Amry Majeed, Brooke Ruane, Crnp, Christine Shusted, Mph, Julie Barta, Md

Health Equity and Quality Improvement (HEQI) Summit

Objectives

• To define the frequency of incidental findings on low-dose CT (LDCT) scans among patients undergoing lung cancer screening.
• To determine the current reporting methods for incidental findings and measure the frequency of clinical follow-up.

Standardized Bronchoscopy Testing For Immunocompromised Patients, C. Nieweld, A. Gandler, K. Biblowitz, B. Menachem, J. Most

Health Equity and Quality Improvement (HEQI) Summit

Aims for Improvement

• Determine the consistency in which the order set was followed
• Determine the length of time from finding pulmonary infiltrate to consultation
• Determine the length of time from consultation to bronchoscopy
• Determine whether a follow up note was written by pulmonary
• Determine whether management is affected based on obtained results

Exploring The Effectiveness Of Asthma Action Plans In Long-Term Asthma Management, Pankhuri Jha, Jessica Most, Md

Health Equity and Quality Improvement (HEQI) Summit

Aims for Improvement

• Determine the efficacy of AAP in helping patients feel more confident in their self-management
• Improve asthma control by at least 10% after receiving an Asthma Action Plan

Linkage Between Poverty And Smoking In Philadelphia And Its Impact On Future Directions For Tobacco Control In The City., Christine S. Shusted, Gregory C. Kane

Department of Medicine Faculty Papers

Poverty is linked to negative health consequences and harmful health behaviors such as smoking. Despite this established correlation, few comparative studies have investigated the relationship between local poverty rates and smoking in urban settings through a Social Ecological Model framework. The authors sought to examine the linkage between local poverty rates in Philadelphia, Pennsylvania and adult smoking rates by scrutinizing existing patterns and potential mediating factors via publicly accessible data in established planning districts. The authors determined several individual, interpersonal, organizational, community, and environmental factors, varying across these districts, that impact smoking in Philadelphia. Poverty rates influence the resources, demographic …

Mitochondrial Quality Control In Age-Related Pulmonary Fibrosis., Willy Roque, Karina Cuevas-Mora, Freddy Romero

Center for Translational Medicine Faculty Papers

Idiopathic pulmonary fibrosis (IPF) is age-related interstitial lung disease of unknown etiology. About 100,000 people in the U.S have IPF, with a 3-year median life expectancy post-diagnosis. The development of an effective treatment for pulmonary fibrosis will require an improved understanding of its molecular pathogenesis and the "normal" and "pathological' hallmarks of the aging lung. An important characteristic of the aging organism is its lowered capacity to adapt quickly to, and counteract, disturbances. While it is likely that DNA damage, chronic endoplasmic reticulum (ER) stress, and accumulation of heat shock proteins are capable of initiating tissue repair, recent studies point …

Improving The Inhaler, Kabir Malkani, Jesse Evensky, Bradley Freid, Alex Reibstein, Gregory C. Kane, Md

Phase 1

Background: It is estimated that about 1 in 10 Americans use inhalers to deliver inhaled drugs for respiratory disease such as COPD and asthma. Some studies have shown that up to 84% of people use their inhaler incorrectly, which can cause long term problems and acute flareups. Therefore, improving the inhaler design to allow for ease of use was the main focus of our project.

Methods: We had a discussion with a pulmonary critical care attending who provided information on proper patient inhaler use and common user errors. He also gave us a sample of different inhalers on the market …

Treatment Of Persistent Air Leaks Using Endobronchial Valves, Michael Zimmerman, Cole Zingas, Achala Donuru, Scott W. Cowan, Nathaniel Evans Iii, Boyd Hehn

Phase 1

Introduction: Persistent air leaks (PAL) are from bronchopleural fistula resulting from communication between the bronchial tree and pleural space. Endobronchial valves (EBVs) are unidirectional valves placed bronchoscopically preventing airflow to the diseased lung lobe. For non-operable patients with PALs, EBVs offer a potential non-invasive treatment approach to stop air leak and allow lung healing. The purpose of this study is to retrospectively analyze EBV placement to treat non-operable adult patients with PALs.

Methods: We retrospectively analyzed all adult patients that underwent EBV placement for PAL treatment at our institution from January 2016 to June 2019. All patients failed conservative …