Respiratory Tract Diseases Commons^™

Heme Metabolism Genes Downregulated In Copd Cachexia, Ava C. Wilson, Preeti L. Kumar, Sool Lee, Margaret M. Parker, Itika Arora, Jarrett D. Morrow, Emiel F.M. Wouters, Richard Casaburi, Stephen I. Rennard, David A. Lomas, Alvar Agusti, Ruth Tal-Singer, Mark T. Dransfield, J. Michael Wells, Surya P. Bhatt, George Washko, Victor J. Thannickal, Hemant K. Tiwari, Craig P. Hersh, Peter J. Castaldi, Edwin K. Silverman, Merry-Lynn N. Mcdonald

Journal Articles: Pulmonary & Critical Care Med

INTRODUCTION: Cachexia contributes to increased mortality and reduced quality of life in Chronic Obstructive Pulmonary Disease (COPD) and may be associated with underlying gene expression changes. Our goal was to identify differential gene expression signatures associated with COPD cachexia in current and former smokers.

METHODS: We analyzed whole-blood gene expression data from participants with COPD in a discovery cohort (COPDGene, N = 400) and assessed replication (ECLIPSE, N = 114). To approximate the consensus definition using available criteria, cachexia was defined as weight-loss > 5% in the past 12 months or low body mass index (BMI) (<  20 kg/m

RESULTS: The prevalence of …

Improving The Evaluation Of Copd Exacerbation Treatment Effects By Accounting For Early Treatment Discontinuations: A Post-Hoc Analysis Of Randomized Clinical Trials., Agnieszka Król, Robert Palmér, Virginie Rondeau, Stephen I. Rennard, Ulf G. Eriksson, Alexandra Jauhiainen

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) clinical trials aimed at evaluating treatment effects on exacerbations often suffer from early discontinuations of randomized treatment. Treatment discontinuations imply a loss of information and should ideally be considered in the statistical analysis of trial results, particularly if the discontinuations are related to the disease or treatment itself. Here, we explore this issue by investigating (1) whether there exists an association between the risks of exacerbation and treatment discontinuation in COPD clinical trials and (2) whether disregarding this association can cause bias in exacerbation treatment effect estimates. We focus on the hypothetical estimand, i.e. …

Agonist-Specific Desensitization Of Pge2-Stimulated Camp Signaling Due To Upregulated Phosphodiesterase Expression In Human Lung Fibroblasts, Francisco J. Nunez, Nancy Schulte, David M. Fogel, Joel Michalski, Stephen I. Rennard, Raymond B. Penn, Myron L. Toews, Rennolds S. Ostrom

Journal Articles: Pulmonary & Critical Care Med

Pulmonary fibrosis is characterized by fibroblasts persisting in an activated form, producing excessive fibrous material that destroys alveolar structure. The second messenger molecule cyclic 3',5'-adenosine monophosphate (cAMP) has antifibrotic properties, and prostaglandin E2 (PGE2) can stimulate cAMP production through prostaglandin E (EP)2 and EP4 receptors. Although EP receptors are attractive therapeutic targets, the effects of long-term exposure to PGE2 have not been characterized. To determine the effects of long-term exposure of lung fibroblasts to PGE2, human fetal lung (HFL)-1 cells were treated for 24 h with 100 nM PGE2 or other cAMP-elevating agents. cAMP levels stimulated by acute exposure to …

Substance Use Disorder, Discrimination, And The Cares Act: Using Disability Law To Strengthen New Protections, Kelly K. Dineen, Elizabeth Pendo

All Faculty Scholarship

The COVID-19 pandemic is having devastating consequences for people with substance use disorders (SUD). SUD is a chronic health condition—like people with other chronic health conditions, people with SUD experience periods of remission and periods of exacerbation and relapse. Unlike people with most other chronic conditions, people with SUD who experience a relapse may face criminal charges and incarceration. They are chronically disadvantaged by pervasive social stigma, discrimination, and structural inequities. People with SUD are also at higher risk for both contracting the SARS-CoV-19 virus and experiencing poorer outcomes. Meanwhile, there are early indications that pandemic conditions have led to …

Employee Testing, Tracing, And Disclosure As A Response To The Coronavirus Pandemic, Matthew T. Bodie, Michael Mcmahon

All Faculty Scholarship

As the COVID-19 pandemic continues to devastate the United States, the federal government has largely failed to implement a national program to prevent and contain the virus. As a result, many employers have undertaken their own workplace coronavirus mitigation efforts. This essay examines, in three parts, the legal framework surrounding employer systems of workplace testing, tracing, and disclosure. It first examines the legal issues surrounding employer-mandated COVID-19 testing and temperature checks, especially issues arising under the Americans with Disabilities Act (ADA) and Health Information Portability and Accountability Act (HIPAA). Regarding employer contact tracing efforts, the essay next reviews the multitude …

The Case For Face Shields: Improving The Covid-19 Public Health Policy Toolkit, Timothy L. Wiemken, Ana Santos Rutschman, Robert Gatter

All Faculty Scholarship

As the United States battles the later stages of the first wave of COVID-19 and faces the prospect of future waves, it is time to consider the practical utility of face shields as an alternative or complement to face masks in the policy guidance. Without face shields specifically noted in national guidance, many areas may be reluctant to allow their use as an alternative to cloth face masks, even with sufficient modification.

In this piece, we discuss the benefits of face shields as a substitute to face masks in the context of public health policy. We further discuss the implications …

Three Cases Of Covid-19 Pneumonia That Responded To Icosapent Ethyl Supportive Treatment, Winston Suh, Ivan Urits, Omar Viswanath, Alan D. Kaye, Haresh Patel, Wade Hall, Jonathan P. Eskander

Ellmer School of Nursing Faculty Publications

BACKGROUND Icosapent ethyl, a form of eicosapentaenoic acid with anti-inflammatory activity, has been approved as an adjunctive treatment with statins in patients with hypertriglyceridemia. Icosapent ethyl is currently undergoing clinical trials to determine its anti-inflammatory effects in patients with coronavirus disease 2019 (COVID-19). This report describes 3 intensive care unit (ICU) patients with moderate to severe COVID-19 pneumonia treated with icosapent ethyl as part of their supportive care who had favorable outcomes.

CASE REPORT Case 1 was a 75-year-old man with a past medical history of hyperlipidemia, hypertension, type 2 diabetes mellitus, obesity, and benign prostatic hyperplasia. Case 2 was …

Multitex Rct - A Multifaceted Intervention Package For Protection Against Cotton Dust Exposure Among Textile Workers - A Cluster Randomized Controlled Trial In Pakistan: Study Protocol, Asaad Ahmed Nafees, Sara De Matteis, Muhammad Masood Kadir, Peter Burney, David Coggon, Sean Semple, Paul Cullinan

Community Health Sciences

Background: In the Pakistani textile industry the prevalence of workplace respiratory illnesses, including byssinosis, is high. The MultiTex RCT study aims to determine the effectiveness of a multifaceted intervention package in reducing dust levels in cotton mills, decreasing the frequency of respiratory symptoms among cotton textile workers, and improving their lung function.
Methods/design: We will conduct a cluster-randomized controlled trial at 28 textile mills in Karachi. The intervention will comprise: training in occupational health for all workers and managers reinforced by regular refresher sessions; the formation of workplace committees to draw up, agree and promote a health and safety plan …

Plasma Cysteine/Cystine And Glutathione/Glutathione Disulfide Redox Potentials In Hiv And Copd Patients., Walter H. Watson, Jeffrey D. Ritzenthaler, Paula Peyrani, Timothy L. Wiemken, Stephen P. Furmanek, Andrea Reyes-Vega, Tom J. Burke, Yuxuan Zheng, Julio A. Ramirez, Jesse Roman

Faculty and Staff Scholarship

Chronic obstructive pulmonary disease (COPD) is prevalent in patients infected with HIV. The purpose of this study was to test the hypothesis that systemic oxidation correlates with loss of lung function in subjects with COPD, and that HIV infection can contribute to creating such an environment. Subjects were recruited at the University of Louisville in the following groups: HIV-infected (n = 36), COPD (n = 32), HIV and COPD (n = 28), and uninfected controls with normal lung function (n = 34). HIV infection was assessed by viral load and CD4 cell counts. Pulmonary function was determined by spirometry …

Cavitary Lesion In An Immunocompromised Adult, Syed Talha Qasmi, Turuvekere Jayaram, Enrique Rincon

Internal Medicine

No abstract provided.

Antibiotic Stewardship And Overcoming Antibiotic Resistance In Upper Respiratory Tract Infections, Katherine Elsass, Austin Hilverding, Steve Blake, Brendan Rasor, Steven N. Leonard

Pharmacy and Wellness Review

Antibiotic resistance has rapidly become one of the most significant challenges facing modern health care. Despite widespread public education efforts by the national government and health organizations worldwide, there remains a significant lack of public understanding of antibiotic resistance, how to prevent it and the implications if the science and health care communities fail to find a solution. The Centers for Disease Control and Prevention (CDC) and the American College of Physicians (ACP) recently published updated guidelines for appropriate antibiotic use in upper respiratory tract infections. These guidelines include several key recommendations for acute bronchitis, pharyngitis and acute rhinosinusitis (including …

Programmed Death Pathway Inhibition: Emerging Therapeutic Options For Treatment Of Advanced Or Refractory Cancers, Katherine Elsass, Morgan Homan, Jana Randolph, Brendan Rasor, David Kinder

Pharmacy and Wellness Review

The programmed death-1 (PD-1) pathway has a significant role in the promotion of immune tolerance. The PD-1 receptor ligands are normally expressed on various inactive immune cells. When cancer cells express these ligands, they are able to interact with active T and B lymphocytes to induce this tolerance. Nivolumab and pembrolizumab are two recently approved agents that act to disrupt this binding and facilitate an immune response against cancer cells. Numerous trials, including KEYNOTE-002 and CheckMate 063, have demonstrated the superior safety and efficacy of these drugs in patients with advanced or refractory cancers. Initially approved for the treatment of …

End Tidal Carbon Dioxide Monitoring (Capnography) In The Cardiac Intensive Care Unit, Madeline Elaine Huff, Kenneth T. Shelton

School of Medicine Publications

Background: Carbon dioxide levels can be monitored throughout the respiratory cycle via capnography. In this way, capnography allows healthcare professionals to follow several respiratory factors in real-time, including respiratory depression, apnea, and hypercapnia. Postoperative patients are subjected to significant harm while receiving sedating medications without appropriate monitoring and intervention. Earlier detection of alterations to ventilation status will better enable providers to more accurately dose medications during procedures, especially in high-risk patient populations.

Methods: Patient selection included post-operative patients in the intensive care unit that were receiving sedation/analgesia, high dose or high frequency opioids, epidural or intrathecal pain management, patients that …

Anxiety Induced Pulmonary Edema: A Rare Occurrence, Anum Akhlaq Md, Neda Shahoori, Alexandra Mary Kelada, Aftab Ahmad

Internal Medicine

No abstract provided.

Relationship Of Patient Self-Administered Copd Assessment Test To Physician Standard Assessment Of Chronic Obstructive Pulmonary Disease In A Family Medicine Residency Training Program, Jessica E. Burchette, Ivy A. Click, Leigh Johnson, S. Alicia Williams, Brett Tyler Morgan

Journal of Patient-Centered Research and Reviews

Assessing the global impact of chronic obstructive pulmonary disease (COPD) on a patient’s life can be difficult to perform in the clinical setting due to time constraints and workflow challenges. The primary objective of this study was to compare disease impact ratings between patient self-administered COPD Assessment Test (CAT) and physician standard office assessment. This prospective study was conducted at a family medicine residency clinic in northeast Tennessee. The study included two study groups: 1) adult patients seen at the clinic during the 3-month study period with an active diagnosis of COPD, and 2) their physicians. Physicians’ assessment of the …

Education-Based Interventions Effects On 30-Day Readmission Rates For Patients With Copd, Gina Hand-Eoloff

Dissertations

Purpose: This Quality Improvement (QI) project evaluated the impact of an existing education-based program for Chronic Obstructive Pulmonary Disease (COPD) and its effect on 30-day readmission rates in one hospital in rural Missouri.

Method: A retrospective chart review was completed on 493 patients with an inclusive diagnosis of COPD from June 1, 2018, to March 31, 2019, using a cohort study design and a two-sample t-test analysis. Additional variables were analyzed to determine if there were predictive factors of an elevated risk of readmission.

Results: The two-sample t-test reveals there is no statistically significant difference between the rates of readmission …

Navigating A Difficult Transition In Pulmonary Arterial Hypertension: A Clinical Case Study, Tina Hyman, Michael Salinero, Francisco Javier Jimenez-Carcamo, Margarita Pallares, Maribel Matos

Nursing & Health Sciences Research Journal

Over the past 20 years, Pulmonary Arterial Hypertension (PAH) patients and providers have seen an increase in options to treat PAH. Currently, there are choices for the delivery of medications approved to treat patients with PAH where at one point the only option was intravenous (IV) therapy. This case study details the transition from IV Epoprostenol to oral Treprostinil for the treatment of a 53 year old female diagnosed with severe Pulmonary Arterial Hypertension whose quality of life became unbearable by the IV medication delivery route. This patient was a synchronized swimmer in her youth and her passion for water …

Provider Education And Rapid Antigen Detection Test Use In An Academic Pediatric Clinic, Steven Dahl

Research Days

No abstract provided.

Impact Of Palliative Care Consultations For Patients Admitted To Maine Medical Center With Acute Exacerbations Of Copd, Benjamin Jarrett, Isabella Strumpf, Rebecca Hutchinson

MaineHealth Maine Medical Center

Background and purpose:

• COPD is the 3rd leading cause of death.

• Specialty Palliative Care (PC) is underutilized in COPD patients.

•PC involvement has been shown to improve quality of life and satisfaction with overall care.

• We sought to evaluate the association of receipt of palliative medicine consultation during an admission for acute exacerbation of COPD with a documented Goals of Care conversations and/or presence of an advanced directive and/or POLST.

Improving Bronchiolitis Care Across Multiple Care Settings Using A Deimplementation Bundle, Amanda Nedved, Kathleen Berg, Troy Richardson, Amanda Montalbano, Matthew B. Johnson

Posters

Despite the availability of a bronchiolitis CPG; variation in care practices still existed at our institution. The aim of our quality improvement (QI) project was to increase overall adherence with our institutional CPG in patients 60 days to 24 months of age diagnosed with bronchiolitis in the urgent care centers (UCC), emergency departments (ED), and general inpatient units from a baseline of 40.9% to 60% by the end of two bronchiolitis seasons.

Physical Exercise – The Friend Or The Enemy Of The Patient With Pulmonary Tuberculosis?, Victoria Maria Ruta, Teodora Gabriela Alexescu, Simina Tarmure, Vasile Negrean, Monica Carmen Pop, Nicoleta Motoc, Iulia Olimpia Pfingstgraf, Mirela Georgiana Perne, Lorena Ciumarnean, Simona Valeria Clichici, Adina Milena Man

Journal of Mind and Medical Sciences

Introduction. Tuberculosis, a major cause of morbidity and mortality, is the second cause of death from an infectious disease, after HIV/AIDS. Each second, a new infection occurs around the globe. Pulmonary tuberculosis can equally affect a performance athlete as well as an aspiring athlete. Physical exercise must be individualized and customized. Pulmonary rehabilitation guides 3 recommend types of exercises for patients with obstructive pathology: stretching, cardiovascular exercise or aerobics. Exercises must be started under medical supervision and must be interrupted if: the ventricular altitude increases above the maximum estimated level for the age, oxygen saturation (SaO2). Aim. The current review …

Direct Lung Sampling Indicates That Established Pathogens Dominate Early Infections In Children With Cystic Fibrosis., Peter Jorth, Zarmina Ehsan Md, Amir Rezayat, Ellen Caldwell, Christopher Pope, John J. Brewington, Christopher H. Goss, Dan Benscoter, John P. Clancy, Pradeep K. Singh

Manuscripts, Articles, Book Chapters and Other Papers

Culture and sequencing have produced divergent hypotheses about cystic fibrosis (CF) lung infections. Culturing suggests that CF lungs are uninfected before colonization by a limited group of CF pathogens. Sequencing suggests diverse communities of mostly oral bacteria inhabit lungs early on and diversity decreases as disease progresses. We studied the lung microbiota of CF children using bronchoscopy and sequencing, with measures to reduce contamination. We found no evidence for oral bacterial communities in lung lavages that lacked CF pathogens. Lavage microbial diversity varied widely, but decreases in diversity appeared to be driven by increased CF pathogen abundance, which reduced the …

Management Of Patients With Brain Metastases From Non-Small Cell Lung Cancer And Adverse Prognostic Features: Multi-National Radiation Treatment Recommendations Are Heterogeneous, Minesh Mehta

All Publications

No abstract provided.

Rethinking Intravenous Catheter Size And Location For Computed Tomography Pulmonary Angiography, Travis Marshall, Nae Meng Chen, Eric Nguyen, David E. Slattery, Tony Zitek

School of Medicine Faculty Research

Introduction: Computed tomography pulmonary angiography (CTPA) is the test of choice for diagnosis of pulmonary embolism (PE) in the emergency department (ED), but this test may be indeterminate for technical reasons such as inadequate contrast filling of the pulmonary arteries. Many hospitals have requirements for intravenous (IV) catheter size or location for CTPAs to reduce the chances of inadequate filling, but there is a lack of clinical data to support these requirements. The objective of this study was to determine if a certain size or location of IV catheter used for contrast for CTPA is associated with an increased chance …

Gene Co-Expression Networks Analysis Reveal Novel Molecular Endotypes In Alpha-1 Antitrypsin Deficiency, Jen-Hwa Chu, Wenlan Zang

Yale Day of Data

Rationale:Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that predisposes to early onset pulmonary emphysema and airways obstruction. The exact mechanism through which AATD leads to lung disease is incompletely understood.

Objectives: To investigate the effect of AAT genotype and augmentation therapy on bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMC) transcriptome, while examining the link between gene expression profiles, and clinical features of AATD.

Methods: We performed RNA-Seq on RNA extracted from BAL and PBMC on samples obtained from 89 AATD patients enrolled in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Differential …

Tgf-Β Induces A Heart Failure Phenotype Via Fibroblasts Exosome Signaling, Hesham Basma, Adelaide N. Johanson, Kajari Dhar, Daniel R. Anderson, Fang Qiu, Stephen I. Rennard, Brian D. Lowes

Journal Articles: Pulmonary & Critical Care Med

PURPOSE: The mechanisms for persistent and progressive loss of myocardial function in advanced heart failure (HF) remain incompletely characterized. In the current study, we sought to determine the impact of TGF-β on fibroblasts transcriptional profiles and assess if exosomes from TGF-β treated fibroblasts could induce a heart failure phenotype in co-cultured cardiomyocytes.

METHOD: Normal heart fibroblasts were treated with TGF-β with a final conc. of 2.5 ng/ml in serum free media. HF fibroblasts were also obtained from patients undergoing implantation of left ventricular assist devices. Exosomes were collected using three-step ultracentrifugation. Cardiomyocytes were co-cultured with exosomes from TGF-β-treated, HF and …

Bronchoalveolar Lavage Fluid From Copd Patients Reveals More Compounds Associated With Disease Than Matched Plasma, Eitan Halper-Stromberg, Lucas Gillenwater, Charmion Cruickshank-Quinn, Wanda Kay O'Neal, Nichole Reisdorph, Irina Petrache, Yonghua Zhuang, Wassim W. Labaki, Jeffrey L. Curtis, James Wells, Stephen I. Rennard, Katherine A. Pratte, Prescott Woodruff, Kathleen A. Stringer, Katerina Kechris, Russell P. Bowler

Journal Articles: Pulmonary & Critical Care Med

Smoking causes chronic obstructive pulmonary disease (COPD). Though recent studies identified a COPD metabolomic signature in blood, no large studies examine the metabolome in bronchoalveolar lavage (BAL) fluid, a more direct representation of lung cell metabolism. We performed untargeted liquid chromatography-mass spectrometry (LC-MS) on BAL and matched plasma from 115 subjects from the SPIROMICS cohort. Regression was performed with COPD phenotypes as the outcome and metabolites as the predictor, adjusted for clinical covariates and false discovery rate. Weighted gene co-expression network analysis (WGCNA) grouped metabolites into modules which were then associated with phenotypes. K-means clustering grouped similar subjects. We detected …

It's More Than Low Bmi: Prevalence Of Cachexia And Associated Mortality In Copd, Merry-Lynn N. Mcdonald, Emiel F.M. Wouters, Erica Rutten, Richard Casaburi, Stephen I. Rennard, David A. Lomas, Marcas Bamman, Bartolome Celli, Alvar Agusti, Ruth Tal-Singer, Craig P. Hersh, Mark Dransfield, Edwin K. Silverman

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Cachexia is associated with increased mortality risk among chronic obstructive pulmonary disease (COPD) patients. However, low body mass index (BMI) as opposed to cachexia is often used, particularly when calculating the BODE (BMI, Obstruction, Dyspnea and Exercise) index. For this reason, we examined mortality using a consensus definition and a weight-loss definition of cachexia among COPD cases and compared two new COPD severity indices with BODE.

METHODS: In the current report, the consensus definition for cachexia incorporated weight-loss > 5% in 12-months or low BMI in addition to 3/5 of decreased muscle strength, fatigue, anorexia, low FFMI and inflammation. The …

Prospective Observational Study In Patients With Obstructive Lung Disease: Novelty Design, Helen K. Reddel, Maria Gerhardsson De Verdier, Alvar Agustí, Gary Anderson, Richard Beasley, Elisabeth H. Bel, Christer Janson, Barry Make, Richard J. Martin, Ian Pavord, David Price, Christina Keen, Asparuh Gardev, Stephen I. Rennard, Alecka Sveréus, Aruna T. Bansal, Lance Brannman, Niklas Karlsson, Javier Nuevo, Fredrik Nyberg, Simon S. Young, Jørgen Vestbo

Journal Articles: Pulmonary & Critical Care Med

Asthma and chronic obstructive pulmonary disease (COPD) have overlapping clinical features and share pathobiological mechanisms but are often considered distinct disorders. Prospective, observational studies across asthma, COPD and asthma-COPD overlap are limited. NOVELTY is a global, prospective observational 3-year study enrolling ∼12 000 patients ≥12 years of age from primary and specialist clinical practices in 19 countries (ClinicalTrials.gov identifier: NCT02760329). NOVELTY's primary objectives are to describe patient characteristics, treatment patterns and disease burden over time, and to identify phenotypes and molecular endotypes associated with differential outcomes over time in patients with a diagnosis/suspected diagnosis of asthma and/or COPD. NOVELTY …

Changes In Muscle Size, Quality And Power Are Related To Physical Function In Patients With Critical Illness, Kirby Mayer

Theses and Dissertations--Rehabilitation Sciences

Patients admitted to intensive care unit (ICU) are known to develop significant impairments in physical function. Patients with critical illness suffer up to 30% reductions in muscle size within the first ten days of admission to the ICU. Muscle strength testing, Medical Research Council-sum score, is current gold-standard to diagnosis ICU-acquired weakness and predicts risk of mortality and long-term physical function. Muscle power different from muscle strength in that it accounts for velocity of movement, is potentially a better independent predictor of function that has not been studied in this population. In addition, we hypothesize that muscle size and quality …