Medical Specialties Commons^™

Contemporary Use Of Balloon Aortic Valvuloplasty In The Era Of Transcatheter Aortic Valve Implantation, Dawn S Hui, David M Shavelle, Mark J Cunningham, Ray V Matthews, Vaughn A Starnes

The Texas Heart Institute Journal

The development of transcatheter aortic valve implantation (TAVI) has increased the use of balloon aortic valvuloplasty (BAV) in treating aortic stenosis. We evaluated our use of BAV in an academic tertiary referral center with a developing TAVI program.

We reviewed 69 consecutive stand-alone BAV procedures that were performed in 62 patients (mean age, 77 ± 10 yr; 62% men; baseline mean New York Heart Association functional class, 3 ± 1) from January 2009 through December 2012. Enrollment for the CoreValve® clinical trial began in January 2011. We divided the study cohort into 2 distinct periods, defined as pre-TAVI (2009–2010) and …

Effect Of Electrocautery On Endothelial Integrity Of The Internal Thoracic Artery: Ultrastructural Analysis With Transmission Electron Microscopy, Burak Onan, Mehmet Yeniterzi, Ismihan Selen Onan, Burak Ersoy, Suheyla Gonca, Elif Gelenli, Seyhun Solakoglu, Ihsan Bakir

The Texas Heart Institute Journal

The internal thoracic artery (ITA) is typically harvested from the chest wall by means of conventional electrocautery. We investigated the effects of electrocautery on endothelial-cell and vessel-wall morphology at the ultrastructural level during ITA harvesting. Internal thoracic artery specimens from 20 patients who underwent elective coronary artery bypass grafting were investigated in 2 groups. The ITA grafts were sharply dissected with use of a scalpel and clips in the control group (n=10) and were harvested by means of electrocautery in the study group (n=10). Each sample was evaluated for intimal, elastic-tissue, muscular-layer, and adventitial changes. Free flow was measured intraoperatively. …

Off-Pump Myocardial Revascularization In A High-Risk Patient With Essential Thrombocythemia, Ahmad K Darwazah, Hamad Madi, Rami Zagha, Yahia Hawash

The Texas Heart Institute Journal

Essential thrombocythemia is a rare type of myeloproliferative disorder. Cerebral, myocardial, and peripheral thrombosis are all frequent complications of the disease.

A 71-year-old man presented with severe coronary artery disease, associated with cerebral vascular ischemic changes and erythromelalgia. His platelet count was 1,486 ×103/μL. The patient underwent successful myocardial revascularization by means of an off-pump technique after his platelet count had been reduced by hydroxycarbamide administration.

We conclude that the use of off-pump cardiopulmonary bypass in high-risk patients with essential thrombocythemia is safe. Reducing platelet count via the administration of hydroxycarbamide and the careful balancing of antiplatelets and anticoagulants is …

Return To Work After Stroke: A Nursing State Of The Science., Catherine Harris, Phd, Mba, Crnp

College of Nursing Faculty Papers & Presentations

There is a lack of research related to return to work (RTW) after acute ischemic stroke. Historically considered a disease of the elderly, acute ischemic stroke studies have not routinely used return to work as an outcome. Major stroke trials have not routinely collected this data as an endpoint. However, the mean age for acute ischemic stroke (AIS) has declined to 69 years of age, while the incidence in patients under the age of 55 has increased to 19%^1-3. Changes in retirement age have also affected RTW as a consideration in stroke patients. Failure to RTW after recovery …

Randomised Clinical Trial: Polyethylene Glycol 3350 With Sports Drink Vs. Polyethylene Glycol With Electrolyte Solution As Purgatives For Colonoscopy--The Incidence Of Hyponatraemia., Rebecca Matro, Constantine Daskalakis, Dan Negoianu, Leo Katz, Cassandra Henry, Michael Share, David Kastenberg

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Polyethylene glycol 3350 plus sports drink (PEG-SD) is a hypo-osmotic purgative commonly used for colonoscopy, though little safety data are available.

AIM: To evaluate the effect of PEG-SD on serum sodium (Na) and other electrolytes compared with PEG-electrolyte solution (PEG-ELS).

METHODS: We performed a single center, prospective, randomised, investigator-blind comparison of PEG-ELS to PEG-SD in out-patients undergoing colonoscopy. Laboratories were obtained at baseline and immediately before and after colonoscopy. The primary endpoint was development of hyponatraemia (Na/L) the day of colonoscopy. Changes in electrolyte levels were computed as the difference between the lowest value on the day of colonoscopy …

Quantification Of Left Atrial Strain And Strain Rate Using Cardiovascular Magnetic Resonance Myocardial Feature Tracking: A Feasibility Study., Johannes Tammo Kowallick, Shelby Kutty, Frank Edelmann, Amedeo Chiribiri, Adriana Villa, Michael Steinmetz, Jan Martin Sohns, Wieland Staab, Nuno Bettencourt, Christina Unterberg-Buchwald, Gerd Hasenfuß, Joachim Lotz, Andreas Schuster

Journal Articles: Cardiology

BACKGROUND: Cardiovascular Magnetic Resonance myocardial feature tracking (CMR-FT) is a quantitative technique tracking tissue voxel motion on standard steady-state free precession (SSFP) cine images to assess ventricular myocardial deformation. The importance of left atrial (LA) deformation assessment is increasingly recognized and can be assessed with echocardiographic speckle tracking. However atrial deformation quantification has never previously been demonstrated with CMR. We sought to determine the feasibility and reproducibility of CMR-FT for quantitative derivation of LA strain and strain rate (SR) myocardial mechanics.

METHODS: 10 healthy volunteers, 10 patients with hypertrophic cardiomyopathy (HCM) and 10 patients with heart failure and preserved ejection …

The Impact Of Waist Circumference On Function And Physical Activity In Older Adults: Longitudinal Observational Data From The Osteoarthritis Initiative, John A. Batsis, Alicia J. Zbehlik, Laura K. Barre, Todd A. Mackenzie, Stephen J. Bartels

Dartmouth Scholarship

Background: We previously demonstrated that BMI is associated with functional decline and reduced quality of life. While BMI in older adults is fraught with challenges, waist circumference (WC) is a marker of visceral adiposity that can also predict mortality. However, its association with function and quality of life in older adults is not well understood and hence we sought to examine the impact of WC on six-year outcomes.

Methods: We identified adults aged ≥60 years from the longitudinal Osteoarthritis Initiative and stratified the cohort into quartiles based on WC. Our primary outcome measures of function at six year follow-up included: …

Nontyphoidal Cardiac Salmonellosis: Two Case Reports And A Review Of The Literature, Daniel Ortiz, Eric M Siegal, Christopher Kramer, Bijoy K Khandheria, Ernesto Brauer

The Texas Heart Institute Journal

Nontyphoidal Salmonella, especially Salmonella enterica, is a rare cause of endocarditis and pericarditis that carries a high mortality rate. Proposed predisposing conditions include immunodeficiency states, congenital heart defects, and cardiac valve diseases. We present 2 cases of cardiovascular salmonellosis. The first case is that of a 73-year-old woman with mechanical mitral and bioprosthetic aortic valves who died from sequelae of nontyphoidal Salmonella mitral valve vegetation, aortic valve abscess, and sepsis. The second case is that of a 62-year-old man with a recent systemic lupus erythematosus exacerbation treated with oral steroids, who presented with obstructive features of tamponade and sepsis secondary …

Intravitreal Triamcinolone Acetonide Injection For Macular Edema Due To Central Retinal Vein Occlusion Persisting Despite Multiple Intravitreal Bevacizumab Injections., Rayan A Alshareef, Sunir Garg, Jason Hsu, James Vander, Carl Park, Marc J Spirn

Wills Eye Hospital Papers

PURPOSE: To evaluate the response to intravitreal triamcinolone acetonide for macular edema persisting or recurring despite multiple intravitreal bevacizumab (IVB) treatments for central retinal vein occlusion (CRVO).

METHODS: Retrospective interventional case series of 21 eyes with CRVO from 21 patients who were diagnosed with persistent or recurrent macular edema secondary to CRVO and treated with 0.1mL (4mg) intravitreal triamcinolone acetonide (IVTA) after initial treatment with 3 or more IVB injections. Anatomic and visual responses were the study primary outcomes.

RESULTS: Mean logarithm of the minimum angle of resolution visual acuity was 1.19 (20/316) immediately before IVTA injection, and improved to …

Safety Of Hexaminolevulinate For Blue Light Cystoscopy In Bladder Cancer. A Combined Analysis Of The Trials Used For Registration And Postmarketing Data., J Alfred Witjes, Leonard G. Gomella, Arnulf Stenzl, Sam S. Chang, Dirk Zaak, H Barton Grossman

Department of Urology Faculty Papers

OBJECTIVE: To detail and put into perspective, safety of hexaminolevulinate blue light cystoscopy (HAL-BLC), including repeated use, based on combined data of controlled trials used for registration of HAL and postmarketing experience.

METHODS: Safety data of 2 randomized comparative studies (group 1) and 4 within patient control studies (group 2) were combined. Postmarketing data from >200,000 patients were analyzed.

RESULTS: In group 1, 533 patients were examined with HAL-BLC and 499 with white light (WL) cystoscopy. In group 2, 791 patients were examined with both WL and HAL-BLC. Between 73% and 93% of these patients had concomitant diseases. Between 41% …

Heuristic Modeling Of Carcinogenesis For The Population With Dichotomous Susceptibility To Cancer: A Pancreatic Cancer Example., Tengiz Mdzinarishvili, Simon Sherman

Journal Articles: Eppley Institute

At present, carcinogenic models imply that all individuals in a population are susceptible to cancer. These models either ignore a fall of the cancer incidence rate at old ages, or use some poorly identifiable parameters for its accounting. In this work, a new heuristic model is proposed. The model assumes that, in a population, only a small fraction (pool) of individuals is susceptible to cancer and decomposes the problem of the carcinogenic modeling on two sequentially solvable problems: (i) determination of the age-specific hazard rate in individuals susceptible to cancer (individual hazard rate) from the observed hazard rate in the …

Treatment Preferences Among Problem Drinkers In Primary Care., Daniel Z Lieberman, Anne Cioletti, Suena H Massey, Rochelle S Collantes, Brad B Moore

Psychiatry and Behavioral Sciences Faculty Publications

OBJECTIVE: Alcohol misuse is common among primary care patients, yet many do not receive treatment because doctors believe problem drinkers are "in denial," or are unwilling to change their drinking habits. The real problem, however, may be that patients are being offered treatment modalities that do not meet their needs. This study was designed to measure the acceptability of various treatment options among drinkers who were currently not receiving treatment.

METHOD: Patients in a primary care clinic were given a self-report questionnaire that included: (1) the Alcohol Use Disorders Questionnaire, (2) a measure of readiness to change drinking behavior, and …

Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio

Sanders-Brown Center on Aging Faculty Publications

Aims: To evaluate the relationship between self-reported head injury and cognitive impairment, dementia, mortality, and Alzheimer's disease (AD)-type pathological changes. Methods: Clinical and neuropathological data from participants enrolled in a longitudinal study of aging and cognition (n = 649) were analyzed to assess the chronic effects of self-reported head injury. Results: The effect of self-reported head injury on the clinical state depended on the age at assessment: for a 1-year increase in age, the OR for the transition to clinical mild cognitive impairment (MCI) at the next visit for participants with a history of head injury was 1.21 and 1.34 …

Sex-Specific Biatrial Volumetric Measurements Obtained With Use Of Multidetector Computed Tomography In Subjects With And Without Coronary Artery Disease, Matthew J Budoff, Sandeep R Pagali, Yasmin S Hamirani, Andy Chen, Gordon Cheu, Yanlin Gao, Dong Li, Songshou Mao

The Texas Heart Institute Journal

Atrial volumetric measurement has proven clinical implications. Advances in cardiac imaging, notably the precision enabled by multidetector computed tomography (MDCT), herald the need for new criteria of what constitutes normal volumetric measurements. With use of 64-slice MDCT, we compared the atrial volumes in healthy individuals with those in individuals with coronary artery disease.

By means of manual segmentation, we measured biatrial volume in 686 participants who underwent retrospective electrocardiographic-gated MDCT angiographic evaluation. The study population included a control group of 203 persons with no cardiac abnormalities, and a study group of 483 patients with obstructive coronary artery disease. All variables …

Natural Progression Of Low-Gradient Severe Aortic Stenosis With Preserved Ejection Fraction, Antony Leslie Innasimuthu, Sanjay Kumar, Jason Lazar, William E Katz

The Texas Heart Institute Journal

Because the natural progression of low-gradient aortic stenosis (LGAS) has not been well defined, we performed a retrospective study of 116 consecutive patients with aortic stenosis who had undergone follow-up echocardiography at a median interval of 698 days (range, 371–1,020 d). All patients had preserved left ventricular ejection fraction (>0.50) during and after follow-up.

At baseline, patients were classified by aortic valve area (AVA) as having mild stenosis (≥1.5 cm2), moderate stenosis (≥1 to <1.5 cm2), or severe stenosis (<1 cm2). Severe aortic stenosis was further classified by mean gradient (LGAS, mean <40 mmHg; high-gradient aortic stenosis [HGAS], mean ≥40 mmHg). We compared baseline and follow-up values among 4 groups: patients with mild stenosis, moderate stenosis, LGAS, and HGAS.

At baseline, 30 patients had mild stenosis, 54 had moderate stenosis, 24 had LGAS, and 8 had HGAS. Compared with the moderate group, the LGAS …

Outpatient Management Of Heart Failure In The United States, 2006-2008, Kailash Mosalpuria, Sunil K Agarwal, Sirin Yaemsiri, Bredy Pierre-Louis, Samir Saba, Rene Alvarez, Stuart D Russell

The Texas Heart Institute Journal

Better outpatient management of heart failure might improve outcomes and reduce the number of rehospitalizations. This study describes recent outpatient heart-failure management in the United States.

We analyzed data from the National Ambulatory Medical Care Survey of 2006–2008, a multistage random sampling of non-Federal physician offices and hospital outpatient departments.

Annually, 1.7% of all outpatient visits were for heart failure (51% females and 77% non-Hispanic whites; mean age, 73 ± 0.5 yr). Typical comorbidities were hypertension (62%), hyperlipidemia (36%), diabetes mellitus (35%), and ischemic heart disease (29%). Body weight and blood pressure were recorded in about 80% of visits, and …

Exertional Dyspnea As A Symptom Of Infrarenal Aortic Occlusive Disease, Stacey L Schott, Fernanda Porto Carreiro, James R Harkness, Mahmoud B Malas, Stephen M Sozio, Sammy Zakaria

The Texas Heart Institute Journal

Advanced atherosclerosis of the aorta can cause severe ischemia in the kidneys, refractory hypertension, and claudication. However, no previous reports have clearly associated infrarenal aortic stenosis with shortness of breath. A 77-year-old woman with hypertension and hyperlipidemia presented with exertional dyspnea. Despite extensive testing and observation, no apparent cause for this patient's dyspnea was found. Images revealed severe infrarenal aortic stenosis. After the patient underwent stenting of the aortic occlusion, she had immediate symptomatic improvement and complete resolution of her dyspnea within one month. Twelve months after vascular intervention, the patient remained asymptomatic. In view of the distinct and lasting …

A Pilot Clinical Trial Of Intravesical Mitomycin-C And External Deep Pelvic Hyperthermia For Non-Muscle-Invasive Bladder Cancer., Brant A Inman, Paul R. Stauffer, Oana A Craciunescu, Paolo F Maccarini, Mark W Dewhirst, Zeljko Vujaskovic

Department of Radiation Oncology Faculty Papers

PURPOSE: This paper aims to evaluate the safety and heating efficiency of external deep pelvic hyperthermia combined with intravesical mitomycin C (MMC) as a novel therapy for non-muscle-invasive bladder cancer (NMIBC).

MATERIALS AND METHODS: We enrolled subjects with bacillus Calmette-Guérin (BCG) refractory NMIBC to an early phase clinical trial of external deep pelvic hyperthermia (using a BSD-2000 device) combined with MMC. Bladders were heated to 42 °C for 1 h during intravesical MMC treatment. Treatments were given weekly for 6 weeks, then monthly for 4 months. Heating parameters, treatment toxicity, and clinical outcomes were systematically measured.

RESULTS: Fifteen patients were …

A Long-Term Study Of The Effects Of Antiviral Therapy On Survival Of Patients With Hbv-Associated Hepatocellular Carcinoma (Hcc) Following Local Tumor Ablation., Hie-Won Hann, Robert Coben, Daniel Brown, Laurence Needleman, Ernest Rosato, Albert Min, Richard Hann, Kyong Bin Park, Stephen Dunn, Anthony J. Dimarino

Department of Medicine Faculty Papers

The ultimate goal of antiviral therapy for chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC). Earlier we reported favorable effects of antiviral therapy on survival of HCC patients following curative tumor ablation (Int J Cancer online 14 April 2010; doi: 10.1002/ijc.25382). It was the first observation made in the United States. We now report 12 year follow-up of this patient group. CHB patients with no prior antiviral therapy with a single HCC (≤ 7 cm) were studied. All patients underwent local tumor ablation as their first option. Patients diagnosed before 1999 received no antiviral treatment while those diagnosed …

Aging Aggravates Nitrate-Mediated Ros/Rns Changes., Qian Fan, Lifen Chen, Shujuan Cheng, Fang Li, Wayne Bond Lau, Le Feng Wang, Jing Hua Liu

Department of Emergency Medicine Faculty Papers

Nitrates are the most frequently prescribed and utilized drugs worldwide. The elderly are a major population receiving nitrate therapy. Both nitrates and aging can increase in vivo reactive oxygen species (ROS) and reactive nitrogen species (RNS). To date, the effects of aging upon nitrate-induced ROS/RNS alteration are unknown. The present study tested the effects of aging upon nitrate-induced ROS/RNS alteration in vivo. 32 adults and 43 elderly unstable angina (UA) patients were subjected to 48 hours of isosorbide dinitrate intravenous injection (50  μg/minutes) in this clinical study. Blood samples were obtained at baseline and conclusion. Outcome measures of oxidative stress …

High-Speed Optical Coherence Tomography As A Reliable Adjuvant Tool To Grade Ocular Anterior Chamber Inflammation., Ann O. Igbre, Mario C. Rico, Sunir Garg

Wills Eye Hospital Papers

PURPOSE: To evaluate the high-speed anterior segment optical coherence tomography (AS-OCT) grading of the AS inflammation in patients with ocular inflammation.

METHODS: A retrospective consecutive case series study. Patients with clinically visible AS inflammation in at least one eye underwent AS-OCT (Visante; Zeiss Meditec) with three to eight line scans per eye, performed by a trained masked examiner. The images were reviewed for hyperreflective spots, noise, and artifact, and these were correlated to clinical examination.

RESULTS: Seventy-eight eyes of 41 patients were imaged. Forty-seven eyes had anterior chamber cells on clinical examination, and 68 had hyperreflective spots visible on AS-OCT. …

Papillary Muscle Repositioning As A Subvalvular Apparatus Preservation Technique In Mitral Stenosis Patients With Normal Left Ventricular Systolic Function, Gokhan Lafci, Kerim Cagli, Omer Faruk Cicek, Kemal Korkmaz, Osman Turak, Alper Uzun, Adnan Yalcinkaya, Adem Diken, Eren Gunertem, Kumral Cagli

The Texas Heart Institute Journal

Subvalvular apparatus preservation is an important concept in mitral valve replacement (MVR) surgery that is performed to remedy mitral regurgitation. In this study, we sought to determine the effects of papillary muscle repositioning (PMR) on clinical outcomes and echocardiographic left ventricular function in rheumatic mitral stenosis patients who had normal left ventricular systolic function.

We prospectively assigned 115 patients who were scheduled for MVR surgery with mechanical prosthesis to either PMR or MVR-only groups. Functional class and echocardiographic variables were evaluated at baseline and at early and late postoperative follow-up examinations. All values were compared between the 2 groups.

The …

A Prospective, Multicenter, Phase I Matched-Comparison Group Trial Of Safety, Pharmacokinetics, And Preliminary Efficacy Of Riluzole In Patients With Traumatic Spinal Cord Injury., Robert G Grossman, Michael G Fehlings, Ralph F Frankowski, Keith D Burau, Diana S L Chow, Charles Tator, Angela Teng, Elizabeth G Toups, James Harrop, Bizhan Aarabi, Christopher I Shaffrey, Michele M Johnson, Susan J Harkema, Maxwell Boakye, James D Guest, Jefferson R Wilson

Department of Neurosurgery Faculty Papers

A prospective, multicenter phase I trial was undertaken by the North American Clinical Trials Network (NACTN) to investigate the pharmacokinetics and safety of, as well as obtain pilot data on, the effects of riluzole on neurological outcome in acute spinal cord injury (SCI). Thirty-six patients, with ASIA impairment grades A-C (28 cervical and 8 thoracic) were enrolled at 6 NACTN sites between April 2010 and June 2011. Patients received 50 mg of riluzole PO/NG twice-daily, within 12 h of SCI, for 14 days. Peak and trough plasma concentrations were quantified on days 3 and 14. Peak plasma concentration (Cmax) and …

Human And Helicobacter Pylori Coevolution Shapes The Risk Of Gastric Disease, Nuri Kodaman, Alvaro Pazos, Barbara G. Schneider, M. Blanca Piazuelo, Robertino Mera, Rafal S. Sobota

Dartmouth Scholarship

Helicobacter pylori is the principal cause of gastric cancer, the second leading cause of cancer mortality worldwide. However, H. pylori prevalence generally does not predict cancer incidence. To determine whether coevolution between host and pathogen influences disease risk, we examined the association between the severity of gastric lesions and patterns of genomic variation in matched human and H. pylori samples. Patients were recruited from two geographically distinct Colombian populations with significantly different incidences of gastric cancer, but virtually identical prevalence of H. pylori infection. All H. pylori isolates contained the genetic signatures of multiple ancestries, with an ancestral African cluster …

Aspirin Use And Knowledge In The Community: A Population- And Health Facility Based Survey For Measuring Local Health System Performance., Gregory A Roth, Catherine W. Gillespie, Ali A Mokdad, Danny D Shen, David W Fleming, Andy Stergachis, Christopher J L Murray, Ali H Mokdad

Pediatrics Faculty Publications

BACKGROUND: Little is known about the relationship between cardiovascular risk, disease and actual use of aspirin in the community.

METHODS: The Measuring Disparities in Chronic Conditions (MDCC) study is a community and health facility-based survey designed to track disparities in the delivery of health interventions for common chronic diseases. MDCC includes a survey instrument designed to collect detailed information about aspirin use. In King County, WA between 2011 and 2012, we surveyed 4633 white, African American, or Hispanic adults (45% home address-based sample, 55% health facility sample). We examined self-reported counseling on, frequency of use and risks of aspirin for …

Non-Emphysematous Chronic Obstructive Pulmonary Disease Is Associated With Diabetes Mellitus, Craig P. Hersh, Barry J. Make, David A. Lynch, R. Graham Barr, Russell P. Bowler, Peter M.A. Calverley, Peter J. Castaldi, Michael H. Cho, Harvey O. Coxson, Dawn L. Demeo, Marilyn G. Foreman, Meilan K. Han, Benjamin J. Harshfield, John E. Hokanson, Sharon Lutz, Joe W. Ramsdell, Elizabeth A. Regan, Stephen I. Rennard, Joyce D. Schroeder, Frank C. Sciurba, Robert M. Steiner, Ruth Tal-Singer, Edwin Van Beek, Edwin K. Silverman, James D. Crapo, Copdgene And Eclipse Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been classically divided into blue bloaters and pink puffers. The utility of these clinical subtypes is unclear. However, the broader distinction between airway-predominant and emphysema-predominant COPD may be clinically relevant. The objective was to define clinical features of emphysema-predominant and non-emphysematous COPD patients.

METHODS: Current and former smokers from the Genetic Epidemiology of COPD Study (COPDGene) had chest computed tomography (CT) scans with quantitative image analysis. Emphysema-predominant COPD was defined by low attenuation area at -950 Hounsfield Units (LAA-950) ≥10%. Non-emphysematous COPD was defined by airflow obstruction with minimal to no emphysema (LAA-950 …

The Association Of Plasma Biomarkers With Computed Tomography-Assessed Emphysema Phenotypes, Brendan J. Carolan, Grant Hughes, Jarrett Morrow, Craig P. Hersh, Wanda K. O'Neal, Stephen I. Rennard, Sreekumar G. Pillai, Paula Belloni, Debra A. Cockayne, Alejandro P. Comellas, Meilan Han, Rachel L. Zemans, Katerina Kechris, Russell P. Bowler

Journal Articles: Pulmonary & Critical Care Med

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a phenotypically heterogeneous disease. In COPD, the presence of emphysema is associated with increased mortality and risk of lung cancer. High resolution computed tomography (HRCT) scans are useful in quantifying emphysema but are associated with radiation exposure and high incidence of false positive findings (i.e., nodules). Using a comprehensive biomarker panel, we sought to determine if there was a peripheral blood biomarker signature of emphysema.

METHODS: 114 plasma biomarkers were measured using a custom assay in 588 individuals enrolled in the COPDGene study. Quantitative emphysema measurements included percent low lung attenuation (%LAA) ≤ …

Randomized Study Of The Safety, Pharmacokinetics, And Bronchodilatory Efficacy Of A Proprietary Glycopyrronium Metered-Dose Inhaler In Study Patients With Chronic Obstructive Pulmonary Disease, Stephen I. Rennard, Charles Fogarty, Colin Reisner, Carlos Fernandez, Tracy Fischer, Michael Golden, Earl St Rose, Patrick Darken, Gregory Tardie, Chadwick Orevillo

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Bronchodilator medications are central to the symptomatic management of chronic obstructive pulmonary disease (COPD). Metered-dose inhalers (MDIs) are the most commonly used devices to deliver treatment to patients with COPD and asthma, comprising approximately 70% of bronchodilator prescriptions. Proprietary porous-particle technology permits the formulation of long-acting muscarinic antagonists, long-acting β2-agonists, and a combination of both in hydrofluoroalkane (HFA) MDIs, providing a solution to formulation challenges inherent to the development of HFA MDIs, which have contributed to the development of dry-powder inhalers.

METHODS: In this randomized, double-blind, 4-period, 6-treatment, placebo- and active-controlled, multicenter, crossover study, 4 ascending single doses of …

Clinical And Computed Tomographic Predictors Of Chronic Bronchitis In Copd: A Cross Sectional Analysis Of The Copdgene Study, Victor Kim, Adam Davey, Alejandro P. Comellas, Meilan K. Han, George Washko, Carlos H. Martinez, David Lynch, Jin Hwa Lee, Edwin K. Silverman, James D. Crapo, Barry J. Make, Gerard J. Criner, The Copdgene® Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic bronchitis (CB) has been related to poor outcomes in Chronic Obstructive Pulmonary Disease (COPD). From a clinical standpoint, we have shown that subjects with CB in a group with moderate to severe airflow obstruction were younger, more likely to be current smokers, male, Caucasian, had worse health related quality of life, more dyspnea, and increased exacerbation history compared to those without CB. We sought to further refine our clinical characterization of chronic bronchitics in a larger cohort and analyze the CT correlates of CB in COPD subjects. We hypothesized that COPD patients with CB would have thicker airways …

Dnah5 Is Associated With Total Lung Capacity In Chronic Obstructive Pulmonary Disease, Jin Hwa Lee, Merry-Lynn N Mcdonald, Michael H. Cho, Emily S. Wan, Peter J. Castaldi, Gary M. Hunninghake, Nathaniel Marchetti, David A. Lynch, James D. Crapo, David A. Lomas, Harvey O. Coxson, Per S. Bakke, Edwin K. Silverman, Craig P. Hersh, The Copdgene And Eclipse Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction. The aim of our study was to identify genetic variants associated with TLC in COPD.

METHODS: We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All subjects were current or ex-smokers …