Respiratory Tract Diseases Commons^™

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 …

Analyzing Networks Of Phenotypes In Complex Diseases: Methodology And Applications In Copd, Jen-Hwa Chu, Craig P. Hersh, Peter J. Castaldi, Michael H. Cho, Benjamin A. Raby, Nan Laird, Russell Bowler, Stephen I. Rennard, Joseph Loscalzo, John Quackenbush, Edwin K. Silverman

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: The investigation of complex disease heterogeneity has been challenging. Here, we introduce a network-based approach, using partial correlations, that analyzes the relationships among multiple disease-related phenotypes.

RESULTS: We applied this method to two large, well-characterized studies of chronic obstructive pulmonary disease (COPD). We also examined the associations between these COPD phenotypic networks and other factors, including case-control status, disease severity, and genetic variants. Using these phenotypic networks, we have detected novel relationships between phenotypes that would not have been observed using traditional epidemiological approaches.

CONCLUSION: Phenotypic network analysis of complex diseases could provide novel insights into disease susceptibility, disease …

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 …

Comparison Of Serum, Edta Plasma And P100 Plasma For Luminex-Based Biomarker Multiplex Assays In Patients With Chronic Obstructive Pulmonary Disease In The Spiromics Study, Wanda K. O'Neal, Wayne Anderson, Patricia V. Basta, Elizabeth E. Carretta, Claire M. Doerschuk, R. Graham Barr, Eugene R. Bleecker, Stephanie A. Christenson, Jeffrey L. Curtis, Meilan K. Han, Nadia N. Hansel, Richard E. Kanner, Eric C. Kleerup, Fernando J. Martinez, Bruce E. Miller, Stephen P. Peters, Stephen I. Rennard, Mary Beth Scholand, Ruth Tal-Singer, Prescott G. Woodruff, David J. Couper, Sonia M. Davis, Spiromics Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: As a part of the longitudinal Chronic Obstructive Pulmonary Disease (COPD) study, Subpopulations and Intermediate Outcome Measures in COPD study (SPIROMICS), blood samples are being collected from 3200 subjects with the goal of identifying blood biomarkers for sub-phenotyping patients and predicting disease progression. To determine the most reliable sample type for measuring specific blood analytes in the cohort, a pilot study was performed from a subset of 24 subjects comparing serum, Ethylenediaminetetraacetic acid (EDTA) plasma, and EDTA plasma with proteinase inhibitors (P100).

METHODS: 105 analytes, chosen for potential relevance to COPD, arranged in 12 multiplex and one simplex platform …

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 …

Influence Of Diet And Obesity On Copd Development And Outcomes, Corrine K. Hanson, Erica P. Rutten, Emiel F.M. Wouters, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

The global increase in the prevalence and incidence of obesity has called serious attention to this issue as a major public health concern. Obesity is associated with many chronic diseases, including cardiovascular disease and diabetes, and recently the role of overweight and obesity in lung disease has received new interest. Independently of obesity, diet also plays a role as a risk factor for many chronic diseases, and evidence is accumulating to support a role for diet in the prevention and management of several lung diseases. Chronic obstructive lung disease is the third-leading cause of death globally, and both obesity and …

Roflumilast And Dyspnea In Patients With Moderate To Very Severe Chronic Obstructive Pulmonary Disease: A Pooled Analysis Of Four Clinical Trials, Stephen I. Rennard, Shawn X. Sun, Stavros Tourkodimitris, Paul Rowe, Udo M. Goehring, Dirk Bredenbröker, Peter M.A. Calverley

Journal Articles: Pulmonary & Critical Care Med

PURPOSE: Breathlessness is a predominant symptom of chronic obstructive pulmonary disease (COPD), making it a valuable outcome in addition to lung function to assess treatment benefit. The phosphodiesterase-4 inhibitor roflumilast has been shown to provide small but significant improvements in dyspnea, as measured by the transition dyspnea index (TDI), in two 1-year studies in patients with severe to very severe COPD.

PATIENTS AND METHODS: To provide a more comprehensive assessment of the impact of roflumilast on dyspnea, post hoc analyses of four 1-year roflumilast studies (M2-111, M2-112, M2-124, and M2-125) in patients with moderate to very severe COPD were conducted. …

Efficacy And Safety Of Fixed-Dose Combinations Of Aclidinium Bromide/Formoterol Fumarate: The 24-Week, Randomized, Placebo-Controlled Augment Copd Study, Anthony D. D'Urzo, Stephen I. Rennard, Edward M. Kerwin, Victor Mergel, Anne R. Leselbaum, Cynthia F. Caracta, Augment Copd Study Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone. The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.

METHODS: In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, …

A Simplified Score To Quantify Comorbidity In Copd, Nirupama Putcha, Milo A. Puhan, M. Bradley Drummond, Meilan K. Han, Elizabeth A. Regan, Nicola A. Hanania, Carlos H. Martinez, Marilyn Foreman, Surya P. Bhatt, Barry Make, Joe Ramsdell, Dawn L. Demeo, R. Graham Barr, Stephen I. Rennard, Fernando Martinez, Edwin K. Silverman, James Crapo, Robert A. Wise, Nadia N. Hansel

Journal Articles: Pulmonary & Critical Care Med

IMPORTANCE: Comorbidities are common in COPD, but quantifying their burden is difficult. Currently there is a COPD-specific comorbidity index to predict mortality and another to predict general quality of life. We sought to develop and validate a COPD-specific comorbidity score that reflects comorbidity burden on patient-centered outcomes.

MATERIALS AND METHODS: Using the COPDGene study (GOLD II-IV COPD), we developed comorbidity scores to describe patient-centered outcomes employing three techniques: 1) simple count, 2) weighted score, and 3) weighted score based upon statistical selection procedure. We tested associations, area under the Curve (AUC) and calibration statistics to validate scores internally with outcomes …

A Divisive Shuffling Approach (Vista) For Gene Expression Analysis To Identify Subtypes In Chronic Obstructive Pulmonary Disease, Jörg Menche, Amitabh Sharma, Michael H. Cho, Ruth J. Mayer, Stephen I. Rennard, Bartolome Celli, Bruce E. Miller, Nick Locantore, Ruth Tal-Singer, Soumitra Ghosh, Chris Larminie, Glyn Bradley, John H. Riley, Alvar Agusti, Edwin K. Silverman, Albert-László Barabási

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: An important step toward understanding the biological mechanisms underlying a complex disease is a refined understanding of its clinical heterogeneity. Relating clinical and molecular differences may allow us to define more specific subtypes of patients that respond differently to therapeutic interventions.

RESULTS: We developed a novel unbiased method called diVIsive Shuffling Approach (VIStA) that identifies subgroups of patients by maximizing the difference in their gene expression patterns. We tested our algorithm on 140 subjects with Chronic Obstructive Pulmonary Disease (COPD) and found four distinct, biologically and clinically meaningful combinations of clinical characteristics that are associated with large gene expression …

Biomarkers In Nsclc Epidermal Growth Factor Receptor Mutations, Suzanne Freidman

The Science Journal of the Lander College of Arts and Sciences

Lung Cancer is the most common global cause of cancer related deaths in men and women (Markus, Alain, 2013). As standard radiation and chemotherapy have proved ineffective, novel target therapies are in the midst of development. This review will analyze the success of the inhibitor drugs targeting the Epidermal Growth Factor Receptor (EGFR) mutation, commonly found amongst Lung Cancer patients. Numerous studies and reviews are utilized to determine the cause of the 10% success rate currently exhibited for these drugs. The L858R and E746-A750 point mutations and deletions respectively, were found prevalent in responsive patients as well as clinical-pathological features …

The Catabolite Control Protein E (Ccpe) Affects Virulence Determinant Production And Pathogenesis Of Staphylococcus Aureus, Torsten Hartmann, Grégory Baronian, Nadine Nippe, Meike Voss, Bettina Schulthess, Christiane Wolz, Janina Eisenbeis, Kerstin Schmidt-Hohagen, Rosmarie Gaupp, Cord Sunderkötter, Christoph Beisswenger, Robert Bals, Greg A. Somerville, Mathias Herrmann, Virginie Molle, Markus Bischoff

School of Veterinary and Biomedical Sciences: Faculty Publications

Carbon metabolism and virulence determinant production are often linked in pathogenic bacteria, and several regulatory elements have been reported to mediate this linkage in Staphylococcus aureus. Previously, we described a novel protein, catabolite control protein E (CcpE) that functions as a regulator of the tricarboxylic acid cycle. Here we demonstrate that CcpE also regulates virulence determinant biosynthesis and pathogenesis. Specifically, deletion of ccpE in S. aureus strain Newman revealed that CcpE affects transcription of virulence factors such as capA, the first gene in the capsule biosynthetic operon; hla, encoding α-toxin; and psmα, encoding the phenol-soluble modulin cluster α. Electrophoretic mobility …

Is Ramelteon Effective In Improving Sleep Quality In Adult Patients With Mild To Moderate Obstructive Breathing Disorders?, Alison L. Fife

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not ramelteon is effective in improving sleep quality in adult patients with mild to moderate obstructive breathing disorders.

STUDY DESIGN: Review of three English studies published from 2007 to 2010; two randomized controlled studies and one randomized crossover study.

DATA SOURCES: The double blind randomized placebo controlled crossover trial, randomized double blind placebo controlled two way crossover study and double blind placebo controlled randomized controlled trial were found using PubMed.

OUTCOMES MEASURED: Each of the studies measured the sleep quality in patients with …

Is Oral Dexamethasone Safe And Effective For Treating Asthma Exacerbations In Pediatric Patients?, Benhamin J. Kunze

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective evidence based medicine review is to determine whether or not a one or two dose regimen of dexamethasone (DEX) is a safe and effective treatment for asthma exacerbations in the pediatric population.

STUDY DESIGN: Review of three English language, primary randomized controlled trials (RCT) published from 2001-2008.

DATA SOURCES: Three RCTs examining the efficacy of DEX either in a single dose or one dose for two days, compared to a traditional five day regimen of prednisone (PRED).

OUTCOMES MEASURED: The studies examined the number of relapses within 10 days of …

Does The Use Of Fascial Manipulative Therapy Help To Improve Overall Asthma Quality Of Life By Descreasing Asthma Symptoms?, Christie Mecouch

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not the use of fascial manipulative therapy helps to improve overall asthma quality of life by decreasing asthma symptoms.

STUDY DESIGN: Review of two randomized controlled trials (RCTs) and one case study, published between 2005-current, all in the English language.

DATA SOURCES: Two randomized controlled trials (RCTs) and one case study, all of which evaluate the effectiveness of fascial manipulative therapy as it pertains to asthma quality of life. All studies were found using PubMed.

OUTCOMES MEASURED: The outcomes measured were an improvement …

Does Sildenafil Improve Physical Function In Patients With Idiopathic Pulmonary Fibrosis?, Tyler R. Mellinger

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not sildenafil improves physical function in patients with idiopathic pulmonary fibrosis.

STUDY DESIGN: Review of 3 primary research studies published in the English language between 2007 and 2010.

DATA SOURCES: Two randomized, double blind, placebo controlled clinical trials, and one open label study analyzing the effect of sildenafil on patients with idiopathic pulmonary fibrosis were found using PubMed.

OUTCOME MEASURED: The primary tool used to assess physical function in patients with idiopathic pulmonary fibrosis, when treated with sildenafil, was a 6-minute walk distance. …

Is Aztreonam Lysine For Inhalation Effective In The Treatment Of Patients With Cystic Fibrosis And Pseudomonas Aeruginosa Airway Infection?, Christine Shevchenko

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not aztreonam lysine for inhalation is effective in the treatment of patients with cystic fibrosis and Pseudomonas aeruginosa airway infection.

STUDY DESIGN: Review of three English language primary randomized controlled trials published in 2008, 2009, and 2011.

DATA SOURCES: Three randomized, double-blind, placebo-controlled studies using Cochrane and Pubmed databases.

OUTCOMES MEASURED: Patient oriented outcomes measured included change in respiratory symptoms measured by the Cystic Fibrosis Questionnaire-Revised and need for additional anti-pseudomonal antibiotics indicative of pulmonary exacerbation.

RESULTS: In both cystic fibrosis (CF) …

Increased Incidence Of Asthma After Previous Infantile Rsv Bronchiolitis Infection, Ellen Adelia Doebler

Physician Assistant Scholarly Project Posters

• Respiratory Syncytial Virus (RSV) is a very common infection in children less than two years of age.

• Asthma is a common respiratory disease in childhood, which may cause frequent hospitalizations.

• The purpose of this study is to determine if infants previously diagnosed with RSV bronchiolitis have an increased incidence of asthma diagnosis compared to infants not diagnosed with RSV.

• The literature review examines correlation studies of both disease processes and explores incidence of asthma in patients previously diagnosed with Respiratory Syncytial Virus bronchiolitis.

• Individuals previously diagnosed with Respiratory Syncytial Virus bronchiolitis have a higher risk …

The Addition Of Tiotropium In Uncontrolled Asthma, Kathryn Gray

Physician Assistant Scholarly Project Posters

• Many patients with asthma have poorly controlled disease despite the use of both an inhaled corticosteroid (ICS) and a long acting beta agonist (LABA).

• The review explored several studies that compared the addition of tiotropium to patients with uncontrolled asthma currently using both a ICA and a LABA to determine if further symptom reduction is obtained along with reduction of exacerbations

• It was found that patients with poorly controlled asthma will benefit from the addition of tiotropium to the current medication regimen of an ICS and a LABA. Tiotropium offers providers an additional disease controlling option in …

Treatment Of Acute Bronchitis In Children With Pelargonium Sidoides, Amber Houge

Physician Assistant Scholarly Project Posters

Bronchitis is one of the most common acute infections affecting pediatric patients. Most cases are caused by viral infections, do not respond to antibiotic therapy, and can take up to 14 days to resolve with supportive therapy. The purpose of this study is to determine if the use of Pelargonium Sidoides (Umcka™, EPs 7630) extract will decrease the duration and severity of symptoms from acute bronchitis in the pediatric population. Pelargonium Sidoides abstract is an extract of an African Geranium that has been used in traditional medicine for centuries. The review of the literature will evaluate multiple randomized controlled trials …