Critical Care Commons^™

Advancements In Left Ventricular Assist Devices To Prevent Pump Thrombosis And Blood Coagulopathy, Grainne Malone, Gerges Abdelsayed, Fianait Bligh, Fatma Al Qattan, Saifullah Syed, Prateepan Varatharajullu, Augustin Msellati, Daniela Mwipatayi, Maimoona Azhar, Saulat Hasnain Fatimi

Section of Cardiothoracic Surgery

Mechanical circulatory support (MCS) devices, such as left ventricular assist devices (LVADs) are very useful in improving outcomes in patients with advanced-stage heart failure. Despite recent advances in LVAD development, pump thrombosis is one of the most severe adverse events caused by LVADs. The contact of blood with artificial materials of LVAD pumps and cannulas triggers the coagulation cascade. Heat spots, for example, produced by mechanical bearings are often subjected to thrombus build-up when low-flow situations impair washout and thus the necessary cooling does not happen. The formation of thrombus in an LVAD may compromise its function, causing a drop …

Post-Intensive Care Syndrome Prevention And Detection In Covid-19 Patients, Bethany Sloane Melega

Student Scholar Showcase

COVID-19 has impacts on patient health beyond the hospital. The trauma that patients, and families of patients, can experience during an admission to an intensive care unit (ICU) can last long after discharge from the ICU and the hospital in general. The psychological and physical impacts of ICU hospitalization can cause patients to experience Post Intensive Care Syndrome (PICS). PICS is the culmination of symptoms that persist after a critical illness that involve all aspects of a patient’s physical and mental well-being and can significantly affect family life and increase recovery time. Due to the strict personal-protective equipment (PPE) usage …

Relationships Of Serum Cc16 Levels With Smoking Status And Lung Function In Copd, Kelli C. Gribben, Jill A. Poole, Amy J. Nelson, Paraskevi A. Farazi, Christopher S. Wichman, Art J. Heires, Debra J. Romberger, Tricia D. Levan

Journal Articles: Pulmonary & Critical Care Med

Background: The club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects, and low CC16 serum levels have been associated with both risk and progression of COPD, yet the interaction between smoking and CC16 on lung function outcomes remains unknown.

Methods: Utilizing cross-sectional data on United States veterans, CC16 serum concentrations were measured by ELISA and log transformed for analyses. Spirometry was conducted and COPD status was defined by post-bronchodilator FEV₁/FVC ratio < 0.7. Smoking measures were self-reported on questionnaire. Multivariable logistic and linear regression were employed to examine associations between CC16 levels and COPD, and lung function with adjustment for covariates. Unadjusted Pearson correlations described relationships between CC16 level and lung function measures, pack-years smoked, and years since smoking cessation.

Results: The study population (N = 351) was mostly male, white, with an average age over 60 years. An interaction between CC16 and smoking status on …

Identifying Individual Medications Affecting Pulmonary Outcomes When Multiple Medications Are Present, Yisha Li, Ran Dai, Yeongjin Gwon, Stephen I. Rennard, Barry J. Make, Dinah Foer, Matthew J. Strand, Erin Austin, Kendra A. Young, John E. Hokanson, Katherine A. Pratte, Rebecca Conway, Gregory L. Kinney, Copdgene Investigators

Journal Articles: Pulmonary & Critical Care Med

No abstract provided.

Updated Perspectives On The Role Of Biomechanics In Copd: Considerations For The Clinician, Jennifer M. Yentes, Wai-Yan Liu, Kuan Zhang, Eric Markvicka, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

Patients with chronic obstructive pulmonary disease (COPD) demonstrate extra-pulmonary functional decline such as an increased prevalence of falls. Biomechanics offers insight into functional decline by examining mechanics of abnormal movement patterns. This review discusses biomechanics of functional outcomes, muscle mechanics, and breathing mechanics in patients with COPD as well as future directions and clinical perspectives. Patients with COPD demonstrate changes in their postural sway during quiet standing compared to controls, and these deficits are exacerbated when sensory information (eg, eyes closed) is manipulated. If standing balance is disrupted with a perturbation, patients with COPD are slower to return to baseline …

Allergic Bronchopulmonary Aspergillosis Misdiagnosed As Smear Negative Pulmonary Tuberculosis; A Retrospective Study From Pakistan, Nousheen Iqbal, Muhammad Dawood Amir Sheikh, Kauser Jabeen, Safia Awan, Muhammad Irfan

Section of Pulmonary & Critical Care

Background: Undiagnosed allergic bronchopulmonary aspergillosis (ABPA) can lead to chronic persistent symptoms. In country like Pakistan where tuberculosis (TB) is endemic, a significant proportion of ABPA patients are misdiagnosed as smear negative TB before reaching a diagnosis of ABPA due to chronicity of symptoms.This lead to empiric use of ATT(Anti-tuberculous therapy) and delay in primary diagnosis. The aim of the study is to determine such proportion of ABPA patients.|
Material and methods: This retrospective study was conducted at the outpatient pulmonology clinic of a tertiary care hospital in Karachi, Pakistan from January 2017 to December 2018. Xpert MTB/Rif, TB smear …

Persistence Of Post-Covid Lung Parenchymal Abnormalities During The Three-Month Follow-Up, Ali Bin Sarwar Zubairi, Anjiya Shaikh, Syed Muhammad Zubair, Akbar Shoukat Ali, Safia Awan, Muhammad Irfan

Section of Pulmonary & Critical Care

Introduction: COVID-19-associated pulmonary sequalae have been increasingly reported after recovery from acute infection. Therefore, we aim to explore the charactersitics of persistent lung parenchymal abnormalities in patients with COVID-19.
Material and methods: An observational study was conducted in patients with post-COVID lung parenchymal abnormalities from April till September 2020. Patients ≥18 years of age with COVID-19 who were diagnosed as post-COVID lung parenchymal abnormality based on respiratory symptoms and HRCT chest imaging after the recovery of acute infection. Data was recorded on a structured pro forma, and descriptive analysis was performed using Stata version 12.1.
Results: A total of 30 …

Post Tuberculosis Radiological Sequelae In Patients Treated For Pulmonary And Pleural Tuberculosis At A Tertiary Center In Pakistan, Syed Muhammad Zubair, Mariyam Gohar Ali, Muhammad Irfan

Section of Pulmonary & Critical Care

Treating tuberculosis (TB) is not the end of the disease because of the wide spectrum of post TB sequelae associated with the disease. There is insufficient data on post TB radiological sequelae. The aim of this study is to evaluate the post TB radiological sequelae on chest x-rays in patients who had completed the treatment for pulmonary and pleural TB at a tertiary care hospital of a high TB burden country. This is a retrospective cross-sectional study conducted on patients treated for pulmonary and pleural TB. Adult patients (18 years or above) with a clinical or microbiological diagnosis of pulmonary …

Factors Motivating Smoking Cessation: A Cross-Sectional Study In A Lower-Middle-Income Country, Russell S. Martins, Muhammad Umer Junaid, Muhammad Sharjeel Khan, Namrah Aziz, Zoha Zahid Fazal, Mariam Umoodi, Fatima Shah, Javaid Ahmed Khan

Medical College Documents

Introduction: Only one-quarter of smokers in Pakistan attempt to quit smoking, and less than 3% are successful. In the absence of any literature from the country, this study aimed to explore factors motivating and strategies employed in successful smoking cessation attempts in Pakistan, a lower-middle-income country.
Methods: A survey was carried out in Karachi, Pakistan, amongst adult (≥ 18 years) former smokers (individuals who had smoked ≥100 cigarettes in their lifetime but who had successfully quit smoking for > 1 month at the time of survey). Multivariable logistic regression, with number of quit attempts (single vs. multiple) as the dependent variable, …

Violence Against Healthcare Workers During The Covid-19 Pandemic: A Review Of Incidents From A Lower-Middle-Income Country, Omaima Anis Bhatti, Hareem Rauf, Namrah Aziz, Russell S. Martins, Javaid Khan

Medical College Documents

Background: Healthcare workers (HCWs) across the globe have met tremendous challenges during the COVID-19 (coronavirus disease 2019) pandemic, such as shortages of personal protective equipment, extensive work hours, and constant fear of catching the virus or transmitting it to loved ones. Adding on to the already existing burnout, an increase in incidents of violence and aggression against HCWs was seen in Pakistan and globally.
Objectives: Primarily to review cases of violence against HCWs in Pakistan, highlighting and comparing the instigating factors seen within the country and globally. Secondly, to enlist possible interventions to counter workplace violence in healthcare during a …

Post Covid-19 Tuberculosis: An Emerging Threat Of Pandemic, Aqusa Zahid, Nousheen Iqbal, Sarosh Moeen, Muhammad Irfan

Section of Pulmonary & Critical Care

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) pandemic has hit the world hard. Millions of people have died due to the infection and several have suffered with what are now known as post COVID-19 squeal. Among these squeals one is immunosuppression which leaves patients prone to severe opportunistic infection. We here report a case of young female who was infected by COVID-19 and later developed cavitary pneumonia which upon investigation turned out to be due to mycobacterium tuberculosis. Through this report we aim to highlight the importance of high index of suspicion for infection like Mycobacterium tuberculosis after …

Latent Traits Of Lung Tissue Patterns In Former Smokers Derived By Dual Channel Deep Learning In Computed Tomography Images, Frank Li, Jiwoong Choi, Chunrui Zou, John D. Newell, Alejandro P. Comellas, Chang Hyun Lee, Hongseok Ko, R. Graham Barr, Eugene R. Bleecker, Christopher B. Cooper, Fereidoun Abtin, Igor Barjaktarevic, David Couper, Meilan Han, Nadia N. Hansel, Richard E. Kanner, Robert Paine, Ella A. Kazerooni, Fernando J. Martinez, Wanda O'Neal, Stephen I. Rennard, Benjamin M. Smith, Prescott G. Woodruff, Eric A. Hoffman, Ching-Long Lin

Journal Articles: Pulmonary & Critical Care Med

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and the traditional variables extracted from computed tomography (CT) images may not be sufficient to describe all the topological features of lung tissues in COPD patients. We employed an unsupervised three-dimensional (3D) convolutional autoencoder (CAE)-feature constructor (FC) deep learning network to learn from CT data and derive tissue pattern-clusters jointly. We then applied exploratory factor analysis (EFA) to discover the unobserved latent traits (factors) among pattern-clusters. CT images at total lung capacity (TLC) and residual volume (RV) of 541 former smokers and 59 healthy non-smokers from the cohort of the SubPopulations …

Small Airway Determinants Of Airflow Limitation In Chronic Obstructive Pulmonary Disease, Vasiliy V. Polosukhin, Sergey S. Gutor, Rui-Hong Du, Bradley W. Richmond, Pierre P. Massion, Pingsheng Wu, Justin M. Cates, Kim L. Sandler, Stephen I. Rennard, Timothy S. Blackwell

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Although a variety of pathological changes have been described in small airways of patients with COPD, the critical anatomic features determining airflow limitation remain incompletely characterised.

METHODS: We examined lung tissue specimens from 18 non-smokers without chronic lung disease and 55 former smokers with COPD for pathological features of small airways that could contribute to airflow limitation. Morphometric evaluation was performed for epithelial and subepithelial tissue thickness, collagen and elastin content, luminal mucus and radial alveolar attachments. Immune/inflammatory cells were enumerated in airway walls. Quantitative emphysema scoring was performed on chest CT scans.

RESULTS: Small airways from patients with …

Genetic Variation In Genes Regulating Skeletal Muscle Regeneration And Tissue Remodelling Associated With Weight Loss In Chronic Obstructive Pulmonary Disease, Preeti Lakshman Kumar, Ava C. Wilson, Alison Rocco, Michael H. Cho, Emily Wan, Brian D. Hobbs, George R. Washko, Victor E. Ortega, Stephanie A. Christenson, Xingnan Li, J. Michael Wells, Surya P. Bhatt, Dawn L. Demeo, Sharon M. Lutz, Harry Rossiter, Richard Casaburi, Stephen I. Rennard, David A. Lomas, Wassim W. Labaki, Ruth Tal-Singer, Russel P. Bowler, Craig P. Hersh, Hemant K. Tiwari, Mark Dransfield, Anna Thalacker-Mercer, Deborah A. Meyers, Edwin K. Silverman, Merry-Lynn N. Mcdonald, Copdgene, Eclipse And Spiromics Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. COPD patients with cachexia or weight loss have increased risk of death independent of body mass index (BMI) and lung function. We tested the hypothesis genetic variation is associated with weight loss in COPD using a genome-wide association study approach.

METHODS: Participants with COPD (N = 4308) from three studies (COPDGene, ECLIPSE, and SPIROMICS) were analysed. Discovery analyses were performed in COPDGene with replication in SPIROMICS and ECLIPSE. In COPDGene, weight loss was defined as self-reported unintentional weight loss > 5% in the past year or low …

The Effect Of Long-Acting Dual Bronchodilator Therapy On Exercise Tolerance, Dynamic Hyperinflation, And Dead Space During Constant Work Rate Exercise In Copd, William W. Stringer, Janos Porszasz, Min Cao, Harry B. Rossiter, Shahid Siddiqui, Stephen I. Rennard, Richard Casaburi

Journal Articles: Pulmonary & Critical Care Med

We investigated whether dual bronchodilator therapy (glycopyrrolate/formoterol fumarate; GFF; Bevespi Aerosphere) would increase exercise tolerance during a high-intensity constant work rate exercise test (CWRET) and the relative contributions of dead space ventilation (V_D/V_T) and dynamic hyperinflation (change in inspiratory capacity) to exercise limitation in chronic obstructive pulmonary disease (COPD). In all, 48 patients with COPD (62.9 ± 7.6 yrs; 33 male; GOLD spirometry stage 1/2/3/4, n = 2/35/11/0) performed a randomized, double blind, placebo (PL) controlled, two-period crossover, single-center trial. Gas exchange and inspiratory capacity (IC) were assessed during cycle ergometry at 80% incremental exercise peak …

Longitudinal Imaging-Based Clusters In Former Smokers Of The Copd Cohort Associate With Clinical Characteristics: The Subpopulations And Intermediate Outcome Measures In Copd Study (Spiromics), Chunrui Zou, Frank Li, Jiwoong Choi, Babak Haghighi, Sanghun Choi, Prathish K. Rajaraman, Alejandro P. Comellas, John D. Newell, Chang Hyun Lee, R. Graham Barr, Eugene Bleecker, Christopher B. Cooper, David Couper, Meilan Han, Nadia N. Hansel, Richard E. Kanner, Ella A. Kazerooni, Eric C. Kleerup, Fernando J. Martinez, Wanda O'Neal, Robert Paine, Stephen I. Rennard, Benjamin M. Smith, Prescott G. Woodruff, Eric A. Hoffman, Ching-Long Lin

Journal Articles: Pulmonary & Critical Care Med

PURPOSE: Quantitative computed tomography (qCT) imaging-based cluster analysis identified clinically meaningful COPD former-smoker subgroups (clusters) based on cross-sectional data. We aimed to identify progression clusters for former smokers using longitudinal data.

PATIENTS AND METHODS: We selected 472 former smokers from SPIROMICS with a baseline visit and a one-year follow-up visit. A total of 150 qCT imaging-based variables, comprising 75 variables at baseline and their corresponding progression rates, were derived from the respective inspiration and expiration scans of the two visits. The COPD progression clusters identified were then associated with subject demography, clinical variables and biomarkers.

RESULTS: COPD severities at baseline …

Angiopoietin 1 Protects Against Lps-Induced Acute Lung Injury And Alveolar Remodeling In Neonatal Mice, Umar Salimi

Research Days

No abstract provided.

Current Smoking With Or Without Chronic Bronchitis Is Independently Associated With Goblet Cell Hyperplasia In Healthy Smokers And Copd Subjects, Victor Kim, Stephanie Jeong, Huaqing Zhao, Mehmet Kesimer, Richard C. Boucher, J. Michael Wells, Stephanie A. Christenson, Meilan K. Han, Mark Dransfield, Robert Paine, Christopher B. Cooper, Igor Barjaktarevic, Russell Bowler, Jeffrey L. Curtis, Robert J. Kaner, Sarah L. O'Beirne, Wanda K. O'Neal, Stephen I. Rennard, Fernando J. Martinez, Prescott G. Woodruff

Journal Articles: Pulmonary & Critical Care Med

COPD, chronic bronchitis (CB) and active smoking have all been associated with goblet cell hyperplasia (GCH) in small studies. Active smoking is strongly associated with CB, but there is a disconnect between CB clinical symptoms and pathology. Chronic cough and sputum production poorly correlate with the presence of GCH or COPD. We hypothesized that the primary determinant of GCH in ever smokers with or without airflow obstruction is active smoking. Goblet Cell Density (GCD) was measured in 71 current or former smokers [32 subjects without COPD and 39 COPD subjects]. Endobronchial mucosal biopsies were stained with Periodic Acid Schiff-Alcian Blue, …

Co-Morbidity Patterns Identified Using Latent Class Analysis Of Medications Predict All-Cause Mortality Independent Of Other Known Risk Factors: The Copdgene® Study, Yisha Li, Margaret Ragland, Erin Austin, Kendra Young, Katherine Pratte, John E. Hokanson, Terri H Beaty, Elizabeth A. Regan, Stephen I. Rennard, Christina Wern, Michael R. Jacobs, Ruth Tal-Singer, Barry J. Make, Gregory L. Kinney, Copdgene Investigators

Journal Articles: Pulmonary & Critical Care Med

PURPOSE: Medication patterns include all medications in an individual's clinical profile. We aimed to identify chronic co-morbidity treatment patterns through medication use among COPDGene participants and determine whether these patterns were associated with mortality, acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and quality of life.

MATERIALS AND METHODS: Participants analyzed here completed Phase 1 (P1) and/or Phase 2 (P2) of COPDGene. Latent class analysis (LCA) was used to identify medication patterns and assign individuals into unobserved LCA classes. Mortality, AECOPD, and the St. George's Respiratory Questionnaire (SGRQ) health status were compared in different LCA classes through survival analysis, logistic …

Blood Eosinophil Counts In Clinical Trials For Chronic Obstructive Pulmonary Disease, Dave Singh, Mona Bafadhel, Christopher E. Brightling, Frank C. Sciurba, Jeffrey L. Curtis, Fernando J. Martinez, Cara B. Pasquale, Debora D. Merrill, Norbert Metzdorf, Stefano Petruzzelli, Ruth Tal-Singer, Christopher Compton, Stephen I. Rennard, Ubaldo J. Martin

Journal Articles: Pulmonary & Critical Care Med

No abstract provided.

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 …

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 …

Imaging-Based Clusters In Former Smokers Of The Copd Cohort Associate With Clinical Characteristics: The Subpopulations And Intermediate Outcome Measures In Copd Study (Spiromics), Babak Haghighi, Sanghun Choi, Jiwoong Choi, Eric A. Hoffman, Alejandro P. Comellas, John D. Newell, Chang Hyun Lee, R. Graham Barr, Eugene Bleecker, Christopher B. Cooper, David Couper, Mei Lan Han, Nadia N. Hansel, Richard E. Kanner, Ella A. Kazerooni, Eric A.C. Kleerup, Fernando J. Martinez, Wanda O'Neal, Robert Paine, Stephen I. Rennard, Benjamin M. Smith, Prescott G. Woodruff, Ching-Long Lin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Quantitative computed tomographic (QCT) imaging-based metrics enable to quantify smoking induced disease alterations and to identify imaging-based clusters for current smokers. We aimed to derive clinically meaningful sub-groups of former smokers using dimensional reduction and clustering methods to develop a new way of COPD phenotyping.

METHODS: An imaging-based cluster analysis was performed for 406 former smokers with a comprehensive set of imaging metrics including 75 imaging-based metrics. They consisted of structural and functional variables at 10 segmental and 5 lobar locations. The structural variables included lung shape, branching angle, airway-circularity, airway-wall-thickness, airway diameter; the functional variables included regional ventilation, …

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 …