Respiratory Tract Diseases Commons^™

A Randomized Placebo-Controlled Trial Of Varenicline For Smoking Cessation Allowing Flexible Quit Dates, Stephen I. Rennard, John Hughes, Paul M. Cinciripini, Eva Kralikova, Tobias Raupach, Carmen Arteaga, Lisa B. St Aubin, Cristina Russ, The Flexible Quit Date Study Group

Journal Articles: Pulmonary & Critical Care Med

INTRODUCTION: Current smoking cessation guidelines recommend setting a quit date prior to starting pharmacotherapy. However, providing flexibility in the date of quitting may be more acceptable to some smokers. The objective of this study was to compare varenicline 1 mg twice daily (b.i.d.) with placebo in subjects using a flexible quit date paradigm after starting medication.

METHODS: In this double-blind, randomized, placebo-controlled international study, smokers of ≥10 cigarettes/day, aged 18-75 years, and who were motivated to quit were randomized (3:1) to receive varenicline 1 mg b.i.d. or placebo for 12 weeks. Subjects were followed up through Week 24. Subjects were …

Persistent Systemic Inflammation Is Associated With Poor Clinical Outcomes In Copd: A Novel Phenotype, Alvar Agustí, Lisa D. Edwards, Stephen I. Rennard, William Macnee, Ruth Tal-Singer, Bruce E. Miller, Jørgen Vestbo, David A. Lomas, Peter M.A. Calverley, Emiel Wouters, Courtney Crim, Julie C. Yates, Edwin K. Silverman, Harvey O. Coxson, Per Bakke, Ruth J. Mayer, Bartolome Celli, Evaluation Of Copd Longitudinally To Identify Predictive Surrogate Endpoints (Eclipse) Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies. To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).

METHODS AND FINDINGS: Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years. We found that, at baseline, 30% of …

Nitric Oxide Metabolites As Biomarkers For Influenza-Like Acute Respiratory Infections Presenting To The Emergency Room, Asad Mian, Federico R Laham, Andrea T Cruz, Harsha Garg, Charles G Macias, A. Chantal Caviness, Pedro A Piedra

Department of Emergency Medicine

Aims: Nitric oxide (NO) is increased in the respiratory tract in pulmonary infections. The aim was to determine whether nasal wash NO metabolites could serve as biomarkers of viral pathogen and disease severity in children with influenza-like illness (ILI) presenting to the emergency department (ED) during the 2009 influenza A H1N1 pandemic.
Methods: Children ≤18 years old presenting to the ED with ILI were eligible. Nasal wash specimens were tested for NO metabolites, nitrate and nitrite, by HPLC and for respiratory viruses by real-time PCR.
Results: Eighty-nine patients with ILI were prospectively enrolled during Oct-Dec, 2009. In the …

Association Of Ireb2 And Chrna3 Polymorphisms With Airflow Obstruction In Severe Alpha-1 Antitrypsin Deficiency., Woo Jin Kim, Alice M. Wood, Alan F. Barker, Mark L. Brantly, Edward J. Campbell, Edward Eden, Gerard Mcelvaney, Stephen I. Rennard, Robert A. Sandhaus, James M. Stocks, James K. Stoller, Charlie Strange, Gerard Turino, Edwin K. Silverman, Robert A. Stockley, Dawn L. Demeo

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: The development of COPD in subjects with alpha-1 antitrypsin (AAT) deficiency is likely to be influenced by modifier genes. Genome-wide association studies and integrative genomics approaches in COPD have demonstrated significant associations with SNPs in the chromosome 15q region that includes CHRNA3 (cholinergic nicotine receptor alpha3) and IREB2 (iron regulatory binding protein 2).We investigated whether SNPs in the chromosome 15q region would be modifiers for lung function and COPD in AAT deficiency.

METHODS: The current analysis included 378 PIZZ subjects in the AAT Genetic Modifiers Study and a replication cohort of 458 subjects from the UK AAT Deficiency National …

Does Tadalafil Improve Exercise Capacitance In Patients Over 12 Years Old With Pulmonary Hypertension?, Erin Chesnavich

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this systematic review is to determine whether or not the oral Phosphodiesterase inhibitor Tadalafil improves exercise capacitance in those over 12 years with pulmonary hypertension.

Study Design: Review of three primary research materials published in English language in 2009. Data Sources: Randomized, controlled, double blind clinical trials found using PubMed, OVID and COCHRANE databases.

Outcome measured: Trials measured 6-minute walking distance and health related quality of life measurements which included: SF-36 (a measure of self reported health status), and the EQ-5D (a patient reported health related quality of life measure), WHO functional class, clinical worsening, and …

Is Afrin (Oxymetazoline) A Safe And Effective Drug In Normal, Healthy Adults With Reference To Nasal Congestion And The Nasal Response?, Allie Rubinstein

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not, “Is Afrin (Oxymetazoline) a safe and effective drug in normal, healthy adults with reference to nasal congestion and the nasal response?”

STUDY DESIGN: Review of three English language primary studies published in 1997, 1999, 2003.

DATA SOURCES: Randomized, controlled studies (double-blind, placebo-controlled) testing the efficacy and safeness of Afrin in comparison to a placebo group, were found using the PubMed database.

OUTCOMES MEASURED: Nasal patency, congestion, degree of nasal blockage, and symptoms (quantity, consistency, color of nasal secretions, turbinate size/color) were measured through patient diary card …

Assessing Two Spirometric Criteria Of Pre-Bronchodilator And Post-Bronchodilator Fev1/Fvc Ratio In Detecting Air Flow Obstruction, Zeeshan Waheed, Muhammad Irfan, Ahmed Suleman Haque, Najmul Hasan Siddiqui, Safia Awan, Beenish Syed, Javaid Khan

Section of Pulmonary & Critical Care

OBJECTIVES: To assess the Pre-bronchodilator criteria and the Post-bronchodilator criteria of FEV1/FVC ratio in diagnosing Airflow obstruction.

METHODS: An observational study was conducted from 1988 to 2006 at the Aga Khan University Hospital Patients referred to the pulmonary function test laboratory for spirometry with bronchodilator reversibility at the hospital during the above said period were enrolled. Forced spirometry was performed according to ATS guidelines. All patients who had pre-bronchodilator criteria of airflow obstruction were analyzed and compared with the post bronchodilator criteria.

RESULTS: A total of 4222 individuals underwent spirometry out of which 4072 individuals were studied. Using the pre …

Evaluation Of The Pilot Program, Pediatric Early Warning Sentinel Surveillance Program (Pewss), And Its Efficacy In Monitoring Pediatric Illness In Clark County, Nevada, Michelle Lee Lutman

UNLV Theses, Dissertations, Professional Papers, and Capstones

The influenza outbreak that occurred during 2009 stimulated the formation of several surveillance programs throughout the country. The majority monitor only influenza; however, there are several other circulating respiratory pathogens, especially within the pediatric community. These other respiratory pathogens cause a variety of illnesses, such as bronchitis, pneumonia, croup, etc. Prior research has provided the medical community with valuable information about respiratory illnesses, especially those which afflict pediatric patients. Areas of knowledge including seasonality, demographics, signs and symptoms, prevention measures, and pathogenicity, have been greatly expanded over the years. This information has been of tremendous help to the medical community …

Executive Summary: The Management Of Community-Acquired Pneumonia In Infants And Children Older Than 3 Months Of Age: Clinical Practice Guidelines By The Pediatric Infectious Diseases Society And The Infectious Diseases Society Of America., John S. Bradley, Carrie L. Byington, Samir S. Shah, Brian Alverson, Edward R. Carter, Christopher Harrison, Sheldon L. Kaplan, Sharon E. Mace, George H. Mccracken, Matthew R. Moore, Shawn D. St Peter, Jana A. Stockwell, Jack T. Swanson, Pediatric Infectious Diseases Society And The Infectious Diseases Society Of America

Manuscripts, Articles, Book Chapters and Other Papers

Evidenced-based guidelines for management of infants and children with community-acquired pneumonia (CAP) were prepared by an expert panel comprising clinicians and investigators representing community pediatrics, public health, and the pediatric specialties of critical care, emergency medicine, hospital medicine, infectious diseases, pulmonology, and surgery. These guidelines are intended for use by primary care and subspecialty providers responsible for the management of otherwise healthy infants and children with CAP in both outpatient and inpatient settings. Site-of-care management, diagnosis, antimicrobial and adjunctive surgical therapy, and prevention are discussed. Areas that warrant future investigations are also highlighted.

How Does Socioeconomic Development Affect Copd Mortality? An Age-Period-Cohort Analysis From A Recently Transitioned Population In China, Jing Chen, Mary Schooling, Janice Mary Johnston, Anthony Johnson Hedley, Sarah Morag Mcghee

Publications and Research

Background
Chronic obstructive pulmonary disease (COPD) is a leading cause of death, particularly in developing countries. Little is known about the effects of economic development on COPD mortality, although economic development may potentially have positive and negative influences over the life course on COPD. We took advantage of a unique population whose rapid and recent economic development is marked by changes at clearly delineated and identifiable time points, and where few women smoke, to examine the effect of macro-level events on COPD mortality.

Methods
We used Poisson regression to decompose sex-specific COPD mortality rates in Hong Kong from 1981 to …

Treatment Outcome Of Multi-Drug Resistant Tuberculosis Treated As Outpatient In A Tertiary Care Center, Zeeshan Waheed, Muhammad Irfan, Ahmed Suleman Haque, Muhammad Owais Khan, Atif Zubairi, Noor Ul Ain, Javaid A. Khan

Section of Pulmonary & Critical Care

INTRODUCTION: Community-based out-patient treatment for multidrug-resistant tuberculosis (MDR TB) is relatively new concept with reported successful outcomes.

OBJECTIVE: To assess the treatment outcomes of HIV negative multidrug-resistant tuberculosis (MDR TB) patients treated as outpatient at a tertiary care center in Karachi, Pakistan.

METHODS: A retrospective observational study of 53 consecutive, culture proven HIV negative MDR TB patients (resistant at least to both Isoniazid (H) and Rifampin(R) treated at Aga Khan University Hospital, Karachi between August 1999 and March 2007. Data were collected on predesigned performa regarding patient’s demography, clinical features, radiological findings, drug sensitivity, treatment and outcome.

RESULTS: A total …

Real-World Comparison Of Two Molecular Methods For Detection Of Respiratory Viruses, Syed Asad Ali, James E. Gern, Tina V. Hartert, Kathryn M. Edwards, Marie R. Griffin, E Kathryn Mille, Tebeb Gebretsadik, Tressa Pappas, Wai Ming Lee, John V. Williams

Department of Paediatrics and Child Health

Background: Molecular polymerase chain reaction (PCR) based assays are increasingly used to diagnose viral respiratory infections and conduct epidemiology studies. Molecular assays have generally been evaluated by comparing them to conventional direct fluorescent antibody (DFA) or viral culture techniques, with few published direct comparisons between molecular methods or between institutions. We sought to perform a real-world comparison of two molecular respiratory viral diagnostic methods between two experienced respiratory virus research laboratories.
Methods: We tested nasal and throat swab specimens obtained from 225 infants with respiratory illness for 11 common respiratory viruses using both a multiplex assay (Respiratory MultiCode-PLx Assay [RMA]) …

Addressing The Challenges Of Reporting On Childhood Asthma In A Changing Health Care System: Building Better Evidence For High Performance, Meagan Lyon, Anne Rossier Markus, Maya Tuchman Gerstein, Sara J. Rosenbaum

Geiger Gibson/RCHN Community Health Foundation Research Collaborative

Childhood asthma is a serious and costly chronic disease that burdens children and families as well as the health care systems that serve them. A key element to improving asthma outcomes is access to timely and useful data that can improve the quality of care and inform programs and policies to best serve those communities most burdened by asthma. This Policy Brief examines the nation’s data collection framework for childhood asthma and considers steps that might be taken to strengthen it, including the development, collection and refinement of community-level data to inform local health care systems. Through a review of …

The Effects Of Computer-Based Education On Children's Knowledge About Asthma, Matyt L. Adler

Evidence-Based Practice Project Reports

Asthma is a global health problem affecting people of all ages that can cause severe limitations when uncontrolled. In the United States, asthma was the most prevalent chronic disease among children and youth in 2008 (U.S. Department of Health and Human Services, 2009). Because day-to-day management of asthma is the responsibility of the child or the parent, education of patients is one of four crucial components to effectively provide quality asthma care. Changes in workload complexities with primary care visits has increased and visit duration decreased, resulting in less available time to address individual patient needs including the education aspect …

Hughes-Stovin Syndrome, Umair Khalid, Taimur Saleem

Section of Pulmonary & Critical Care

Hughes-Stovin Syndrome (HSS) is a very rare clinical disorder characterized by thrombophlebitis and multiple pulmonary and/or bronchial aneurysms. Less than 40 published cases of HSS have been described in English medical literature so far. The exact etiology and pathogenesis of HSS is unknown, possible causes include infections and angiodysplasia. HSS has also been considered as a variant of Behcet's disease (BD). Patients with HSS usually present with cough, dyspnea, fever, chest pain and haemoptysis. The management of HSS can either be medical or surgical. Medical management includes the use of steroids and cytotoxic agents. Cyclophosphamide, in particular, is a favored …

Negative Pressure Pulmonary Oedema: A Rare Complication Following General Anaesthesia, Zeeshan Waheed, Javaid Khan

Section of Pulmonary & Critical Care

An important cause of pulmonary oedema is Negative Pressure Pulmonary Oedema (NPPE) which characteristically develops soon after extubation from an endo-tracheal intubation. In this case report we identified a case of previously healthy man who was intubated for General Anaesthesia for extraction of impacted molar tooth. Soon after extubation he developed severe respiratory distress. Immediate diagnosis of NPPE secondary to post extubation laryngospasm was made. He was promptly treated with 100 percent oxygen via CPAP (continuous positive airway pressure) mask and within an hour he markedly improved and subsequently became asymptomatic. NPPE is an important cause of morbidity and need …

Causes Of Smoking In Pakistan: An Analysis Of Social Factors, Sobia Nizami, Zain A Sobani, Emmon Raza, Noor-Ul-Ain Baloch, Javaid Khan

Section of Pulmonary & Critical Care

OBJECTIVE: To determine the factors contributing to the initiation and propagation of smoking in visitors to a major tertiary health center in Karachi, Pakistan.

METHODS: Seven major contributing factors to the initiation and propagation of smoking were presented to consenting study participants (n=170) in a questionnaire. Participants were then requested to use their experience and opinion to rate each of the given factors on a scale of 1 to 5 regarding its importance as a causative factor in the initiation and propagation of smoking. Results were analyzed using SPSSv16.0.

RESULTS: Preliminary analysis revealed occupational stress relief as the most important …

Efficacy And Safety Of Once-Daily Aclidinium In Chronic Obstructive Pulmonary Disease, Paul W. Jones, Stephen I. Rennard, Alvar Agusti, Pascal Chanez, Helgo Magnussen, Leonardo Fabbri, James F. Donohue, Eric D. Bateman, Nicholas J. Gross, Rosa Lamarca, Cynthia Caracta, Esther Garcia Gil

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

METHODS: In two double-blind, 52-week studies, ACCLAIM/COPD I (n=843) and II (n=804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70% and FEV1< 80% of the predicted value. The primary endpoint was trough FEV1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George's Respiratory Questionnaire (SGRQ) and time to first moderate or severe COPD exacerbation.

RESULTS: At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p< 0.001) and ACCLAIM/COPD II (by 63 and 59 mL; both p< 0.001). More patients had a SGRQ improvement≥4 units at 52 weeks with aclidinium versus placebo in ACCLAIM/COPD I (48.1% versus 39.5%; p=0.025) and ACCLAIM/COPD II (39.0% versus 32.8%; p=0.074). The time to first exacerbation was significantly delayed by aclidinium in ACCLAIM/COPD II (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.55 to 0.92; p=0.01), but not ACCLAIM/COPD I (HR 1.0; 95% CI 0.72 to 1.33; p=0.9). Adverse events were minor in both studies.

CONCLUSION: Aclidinium is effective and well tolerated …

Reduction Of Exacerbations By The Pde4 Inhibitor Roflumilast--The Importance Of Defining Different Subsets Of Patients With Copd, Stephen I. Rennard, Peter M.A. Calverley, Udo M. Goehring, Dirk Bredenbröker, Fernando J. Martinez

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: As chronic obstructive pulmonary disease (COPD) is a heterogeneous disease it is unlikely that all patients will benefit equally from a given therapy. Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, has been shown to improve lung function in moderate and severe COPD but its effect on exacerbations in unselected populations was inconclusive. This led to the question of whether a responsive subset existed that could be investigated further.

METHODS: The datasets of two previous replicate, randomized, double-blind, placebo-controlled, parallel-group studies (oral roflumilast 500 μg or placebo once daily for 52 weeks) that were inconclusive regarding exacerbations were combined in …

Differentiation Of Embryonic Stem Cells Into Fibroblast-Like Cells In Three-Dimensional Type I Collagen Gel Cultures, Shinsaku Togo, Tadashi Sato, Hisatoshi Sugiura, Xingqi Wang, Hesham Basma, Amy J. Nelson, Xiangde Liu, Tom W. Bargar, J. Graham Sharp, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

Fibroblasts are heterogeneous mesenchymal cells that play important roles in the production and maintenance of extracellular matrix. Although their heterogeneity is recognized, progenitor progeny relationships among fibroblasts and the factors that control fibroblast differentiation are poorly defined. The current study was designed to develop a reliable method that would permit in vitro differentiation of fibroblast-like cells from human and murine embryonic stem cells (ESCs). Undifferentiated ESCs were differentiated into embryoid bodies (EBs) with differentiation media. EBs were then cast into type I collagen gels and cultured for 21 d with basal media. The spindle-shaped cells that subsequently grew from the …