Critical Care Commons^™

Sputum Neutrophils As A Biomarker In Copd: Findings From The Eclipse Study, Dave Singh, Lisa Edwards, Ruth Tal-Singer, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

INTRODUCTION: The percentage of neutrophils in sputum are increased in COPD patients, and may therefore be a biomarker of airway inflammation. We studied the relationships between sputum neutrophils and FEV1, health status, exacerbation rates, systemic inflammation and emphysema, and long term variability at 1 year.

METHODS: Sputum samples were obtained from 488 COPD patients within the ECLIPSE cohort. 359 samples were obtained at baseline, and 297 after 1 year. 168 subjects provided samples at both visits. Serum interleukin-6 (IL-6), IL-8, surfactant protein D and C-reactive protein levels were measured by immunoassays. Low-dose CT scans evaluated emphysema.

RESULTS: Sputum neutrophil % …

Characterisation Of Copd Heterogeneity In The Eclipse Cohort, Alvar Agusti, Peter M.A. Calverley, Bartolome Celli, Harvey O. Coxson, Lisa D. Edwards, David A. Lomas, William Macnee, Bruce E. Miller, Steve I. Rennard, Edwin K. Silverman, Ruth Tal-Singer, Emiel Wouters, Julie C. Yates, Jørgen Vestbo, The Evaluation Of Copd Longitudinally To Identify Predictive Surrogate Endpoints (Eclipse) Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations. This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).

METHODS: We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers. In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.

RESULTS: COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function. Co-morbidities were more prevalent in COPD patients than in …

Ccl2 Responses To Mycobacterium Tuberculosis Are Associated With Disease Severity In Tuberculosis, Zahra Hasan, Jacqueline M. Cliff, Hazel M. Dockrell, Bushra Jamil, Muhammad Irfan, Mussarat Ashraf, Rabia Hussain

Section of Pulmonary & Critical Care

Background

Leucocyte activating chemokines such as CCL2, CCL3, and CXCL8 together with proinflammatory IFNγ, TNFα and downmodulatory IL10 play a central role in the restriction of M. tuberculosis infections, but is unclear whether these markers are indicative of tuberculosis disease severity.

Methodology

We investigated live M. tuberculosis- and M. bovis BCG- induced peripheral blood mononuclear cell responses in patients with tuberculosis (TB) and healthy endemic controls (ECs, n = 36). TB patients comprised pulmonary (PTB, n = 34) and extrapulmonary groups, subdivided into those with less severe localized extrapulmonary TB (L-ETB, n = 16) or severe disseminated ETB (D-ETB, …

Treatment Outcome Of Multi-Drug Resistant Tuberculosis In A Tertiary Care Hospital In Karachi, Nisar Ahmed Rao, Zeeshan Mahfooz, Muhammad Irfan

Section of Pulmonary & Critical Care

Objective: To assess the outcomes of pulmonary multidrug-resistant tuberculosis (MDR-TB) patients treated at Ojha Institute of Chest Diseases (OICD), a reference hospital for TB in Karachi, Pakistan. Methods: Clinical study for the period 1996-2006, with follow-up until June 2007 was performed. All the culture and sensitivity proven cases of MDR pulmonary TB were initially admitted for 3-6 months till the sputum converted negative. Treatment regimen was decided on individual basis, and included 4-6 drugs. Supervised treatment was given to all patients during the hospitalization. After discharge from the hospital, patients were followed at monthly interval at the outpatient department of …

A Genome-Wide Association Study In Chronic Obstructive Pulmonary Disease (Copd): Identification Of Two Major Susceptibility Loci, Sreekumar G. Pillai, Dongliang Ge, Guohua Zhu, Xiangyang Kong, Kevin V. Shianna, Anna C. Need, Sheng Feng, Craig P. Hersh, Per Bakke, Amund Gulsvik, Andreas Ruppert, Karin C. Lødrup Carlsen, Allen Roses, Wayne Anderson, Stephen I. Rennard, David A. Lomas, Edwin K. Silverman, David B. Goldstein, Icgn Investigators

Journal Articles: Pulmonary & Critical Care Med

There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD). The only known genetic risk factor is severe deficiency of alpha(1)-antitrypsin, which is present in 1-2% of individuals with COPD. We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study. The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial …

One-Year Treatment With Mometasone Furoate In Chronic Obstructive Pulmonary Disease, Peter M.A. Calverley, Stephen I. Rennard, Harold S. Nelson, Jill P. Karpel, Eduardo H. Abbate, Paul Stryszak, Heribert Staudinger

Journal Articles: Pulmonary & Critical Care Med

Many patients with chronic obstructive pulmonary disease (COPD) are treated with twice daily (BID) inhaled corticosteroids (ICS). This study evaluated whether daily PM mometasone furoate administered via a dry powder inhaler (MF-DPI) was equally effective compared to twice daily dosing.In a 52-week, randomized, double-blind, placebo-controlled study, 911 subjects with moderate-to-severe COPD managed without ICS received MF-DPI 800 microg QD PM, MF-DPI 400 microg BID, or placebo. The change from baseline in postbronchodilator forced expiratory volume in 1 second (FEV1), total COPD symptom scores, and health status as well as the percentage of subjects with a COPD exacerbation were assessed. Adverse …

Chest Radiographs In Acute Pulmonary Embolism, Ali Bin Sarwar Zubairi, Shahid Javed Husain, Muhammad Irfan, Kulsoom Fatima, Muhammad Atif Zubairi, Muhammad Islam

Section of Pulmonary & Critical Care

Background: Pulmonary embolism (PE) is a serious clinical entity carrying significant morbidity and mortality. Clinically, it is a difficult condition to diagnose and remains under treated condition in Pakistan due to non-availability of objective tests and lack of awareness among physicians.This study was conducted to determine the chest radiographic presentation in known cases of acute PE presenting to a tertiary care hospital.
Methods: Hospital records of patients with a diagnosis of acute PE were reviewed from June 2000 until June 2004. Fifty diagnosed cases of acute PE on Spiral Computed tomography (CT) of the chest demonstrating an intraluminal-filling defect were …

Broncho Alveolar Carcinoma (B.A.C.), Ahmed N. Abbasi, Muhammad Irfan, Syed Arsalan Raza

Section of Pulmonary & Critical Care

No abstract provided.

Tgf-Beta1 And Serum Both Stimulate Contraction But Differentially Affect Apoptosis In 3d Collagen Gels, Tetsu Kobayashi, Xiangde Liu, Hui Jung Kim, Tadashi Kohyama, Fu-Qiang Wen, Shinji Abe, Qiuhong Fang, Yun Kui Zhu, John R. Spurzem, Peter Bitterman, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

Apoptosis of fibroblasts may be key for the removal of cells following repair processes. Contraction of three-dimensional collagen gels is a model of wound healing and remodeling. Here two potent inducers of contraction, TGF-beta1 and fetal calf serum (FCS) were evaluated for their effect on fibroblast apoptosis in contracting collagen gels. Human fetal lung fibroblasts were cultured in floating type I collagen gels, exposed to TGF-beta1 or FCS, and allowed to contract for 5 days. Apoptosis was evaluated using TUNEL and confirmed by DNA content profiling. Both TGF-beta1 and serum significantly augmented collagen gel contraction. TGF-beta1 also increased apoptosis assessed …

Platelets Stimulate Fibroblast-Mediated Contraction Of Collagen Gels, Ulrika Zagai, Karin Fredriksson, Stephen I. Rennard, Joachim Lundahl, C. Magnus Sköld

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Platelets are thought to play a role in a variety of inflammatory conditions in the lung, some of which may lead to fibrosis. In the current study we tested the hypothesis that whole platelets and platelet lysate can mediate remodelling of extracellular matrix in vitro by affecting fibroblast-mediated contraction of a collagen gel. We also sought to determine to what extent platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) contribute to this effect.

METHODS: Washed platelets, isolated from healthy blood donors, and platelet lysate (freezing and thawing), were cast together with human lung fibroblasts in three-dimensional collagen gels. …

Differences Between Blacks And Whites With Coronary Heart Disease In Initial Symptoms And In Delay In Seeking Care, Sally B. Richards, Marjorie Funk, Kerry A. Milner

Nursing Faculty Publications

BACKGROUND: Mortality rates for coronary heart disease are higher in blacks than in whites. OBJECTIVES: To examine differences between blacks and whites in the manifestation of symptoms of coronary heart disease and in delay in seeking treatment. METHODS: Patients were directly observed as they came to an emergency department with symptoms suggestive of coronary heart disease. The sample included 40 blacks and 191 whites with a final diagnosis of angina or acute myocardial infarction. RESULTS: After controlling for pertinent demographic and clinical characteristics, logistic regression analysis revealed that blacks were more likely than whites to have shortness of breath (odds …

Repair Of The Airway Epithelium: Potential Opportunities For Therapeutic Intervention In Airway Disease, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

The epithelium of the airway has considerable capacity to undergo repair. These repair processes are responsible for maintaining and restoring function after injury of the airways, which likely occurs often as a result of infectious, toxic or other exposures. However, repair processes need not be fully effective. Inadequate repair can take a number of forms and may result in metaplasia, hyperplasia or fibrotic scarring. It is likely that repair processes that lead to tissue disruption play an important role in the chronic airways diseases, such as asthma and bronchitis. Through delineation of these processes, it may become feasible to target …

Efficient Vasoactive Intestinal Polypeptide Hydrolyzing Autoantibody Light Chains Selected By Phage Display, Sonia Tyutyulkova, Qing-Sheng Gao, Austin Thompson, Stephen I. Rennard, Sudhir Paul

Journal Articles: Pulmonary & Critical Care Med

An immunoglobulin light chain (L chain) library derived from the peripheral blood lymphocytes of a patient with asthma was cloned into a phagemid vector. Phage particles displaying L chains capable of binding vasoactive intestinal polypeptide (VIP) were isolated by affinity chromatography. Two VIP binding L chains were expressed in Escherichia coli in soluble form and purified to electrophoretic homogeneity by metal chelating and protein L affinity chromatography. Both L chains catalyzed the hydrolysis of [tyr10-125I]VIP substrate. The catalytic activity eluted at the molecular mass of the monomer form of the L chain (28 kDa) from a gel filtration column. The …