Critical Care Commons^™

Effect Of Budesonide On Fibroblast-Mediated Collagen Gel Contraction And Degradation, Qiuhong Fang, Nancy A. Schulte, Huijung Kim, Tetsu Kobayashi, Xingqi Wang, Anna Miller-Larsson, Elisabet Wieslander, Myron L. Toews, Xiangde Liu, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: The balance between production and degradation of extracellular matrix is crucial in maintaining normal tissue structure. This study was designed to investigate the effect of budesonide on fibroblast-mediated tissue repair and remodeling.

METHODS: Using human fetal lung fibroblasts in a three-dimensional collagen gel culture system, we investigated the effect of budesonide (1-1000 nM) on collagen gel contraction and degradation in the presence or absence of Inflammatory cytokines (interleukin-1β and tumor necrosis factor α; 5 ng/mL each) and, in order to activate latent proteases, serine protease trypsin 0.25 μg/mL. The effects of budesonide on metalloproteinase production and activation were also …

Evaluation Of Vancomycin Dosing And Corresponding Drug Concentrations In Neonatal Intensive Care Unit (Nicu) Patients, Christine Lam Pharmd, Jenny Boucher Bs, Pharmd, Jd, Bcps

Department of Pharmacy

No abstract provided.

Pge 2 Desensitizes Β -Agonist Effect On Human Lung Fibroblast-Mediated Collagen Gel Contraction Through Opregulating Pde4, Qiuhong Fang, Yingmin Ma, Jing Wang, Joel Michalski, Stephen I. Rennard, Xiangde Liu

Journal Articles: Pulmonary & Critical Care Med

In the current study, we investigated the effect of a long-acting β -agonist (salmeterol) and a phosphodiesterase 4 (PDE4) inhibitor (cilomilast) on human lung fibroblast-mediated collagen gel contraction. Higher concentrations of salmeterol (10(-7) and 10(-6) M) inhibited fibroblast-mediated collagen gel contraction. No effect was observed with cilomilast alone (up to 10(-5) M). In the presence of 10(-8) M salmeterol, however, cilomilast could significantly inhibit fibroblast-mediated collagen gel contraction in a concentration-dependent manner (10(-7) ~10(-5) M). Blockade of endogenous PGE2 by indomethacin further potentiated the inhibitory effect of salmeterol on fibroblast-mediated collagen gel contraction, but it did not affect cilomilast's effect. …

Factors Associated Within 28 Days In-Hospital Mortality Of Patients With Acute Respiratory Distress Syndrome, Nadia Sharif, Muhammad Irfan, Javaid Hussain, Javaid Khan

Section of Pulmonary & Critical Care

Objective. To determine the factors leading to in-hospital mortality within 28 days in hospitalized patients with ARDS. It was a prospective observational cohort study conducted in Intensive Care Unit of Aga Khan University Hospital Karachi from March to August 2011. Methodology. Data was collected from patients admitted in the intensive care unit on the basis of inclusion and exclusion criteria. The patients were followed daily for 28 days to record any in-hospital complications and the outcome of patients. Results. Total of 46 patients were included during this period out of which 56% (26) were males and 43% (20) were females. …

Bronchial Carcinoid Presenting As Multiple Lung Abscesses, Zeeshan Waheed, Muhammad Irfan, Saulat Fatimi, Ruqaiya Shahid

Section of Pulmonary & Critical Care

Bronchial carcinoid tumours is a rare group of pulmonary malignant neoplasm that is derived from neuroendocrine system. Bronchial carcinoid usually present with hilar masses, atelactasis, bronchiectasis, or post-obstructive pneumonia. This case describes a very unusual presentation of bronchial carcinoid tumour with multiple lung abscesses involving the whole lung. This report is of an adult lady who presented with multiple lung abscesses involving her whole of the right lung. She was found to have an endo-bronchial lesion in her right main bronchus which eventually turned out to be carcinoid tumour. She responded to resection and antibiotic therapy.

Expression Of M. Tuberculosis-Induced Suppressor Of Cytokine Signaling (Socs) 1, Socs3, Foxp3 And Secretion Of Il-6 Associates With Differing Clinical Severity Of Tuberculosis, Kiran I. Masood, Martin E. Rottenberg, Naseem Salahuddin, Muhammad Irfan, Nisar Rao, Berit Carow, Muniba Islam, Rabia Hussain, Zahra Hasan

Section of Pulmonary & Critical Care

Background

Appropriate immune activation of T cells and macrophages is central for the control of Mycobacterium tuberculosis infections. IFN-γ stimulated responses are lowered in tuberculosis (TB), while expression of Suppressor of Cytokine Signaling (SOCS) molecules – 1 and 3 and CD4⁺CD25⁺FoxP3⁺T regulatory cells is increased. Here we investigated the association of these molecules in regard to clinical severity of TB.

Methods

Peripheral blood mononuclear cells (PBMCs) were isolated from patients with pulmonary TB (PTB, n = 33), extra-pulmonary TB (ETB, n = 33) and healthy endemic controls (EC, n = 15). Cases were classified …

Anti-Inflammatory Effects Of Budesonide In Human Lung Fibroblast Are Independent Of Histone Deacetylase 2, Xingqi Wang, Amy J. Nelson, Zachary M. Weiler, Amol Patil, Tadashi Sato, Nobuhiro Kanaji, Masanori Nakanishi, Joel Michalski, Maha Farid, Hesham Basma, Tricia D. Levan, Anna Miller-Larsson, Elisabet Wieslander, Kai-Christian Muller, Olaf Holz, Helgo Magnussen, Klaus F. Rabe, Xiangde Liu, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

OBJECTIVE AND DESIGN: Reduced expression of histone deacetylase 2 (HDAC2) in alveolar macrophages and epithelial cells may account for reduced response of chronic obstructive pulmonary disease (COPD) patients to glucocorticoids. HDAC2 expression and its role in mediating glucocorticoid effects on fibroblast functions, however, has not been fully studied. This study was designed to investigate whether HDAC2 mediates glucocorticoid effects on release of inflammatory cytokines and matrix metalloproteinases (MMPs) from human lung fibroblasts.

METHODS: Human lung fibroblasts (HFL-1 cells) were stimulated with interleukin (IL)-1 β plus tumor necrosis factor (TNF)-α in the presence or absence of the glucocorticoid budesonide. Cytokines (IL-6 …

B-Type Natriuretic Peptide (Bnp): A Potential Biomarker For Extubation Failure In Infants Following Cardiac Surgery, Jennifer Flint, Lori Erickson, Dawn Tucker, Erica Molitor-Kirsch

Posters

Background: BNP is a hormone released from the cardiac ventricles in response to increased pressure and volume overload1 and is an important biomarker in heart failure. Following congenital heart surgery, elevated BNP levels correlate with longer duration of mechanical ventilation, low cardiac output syndrome, and increased ICU length of stay2-4 Mechanical ventilation (MV) has an exaggerated impact on cardiopulmonary interactions in children with myocardial dysfunction, and extubation readiness can be difficult to determine post-operatively following congenital heart surgery.

Hypothesis: An increase in post-extubation BNP levels can predict extubation failure and the need for reintubation within 48 hours.

Methods:

Design: prospective, …

Having A Greater Proportion Of Registered Nurses In A Respiratory Care Centre Is Associated With Fewer Urinary Infections And Increased Successful Ventilator Weaning, Diane E. Twigg

Research outputs 2013

This study explored the impact of skill mix model changes on patient outcomes in a critical care environment, specifically, a respiratory care centre based in a southern Taiwan medical centre. It identified that the cost of ventilator-dependent patients in Taiwan in 1999 was 3.5 billion New Taiwan dollars, equivalent to US$ 121 million. In this context, controlling the costs of healthcare while maintaining quality care became critical. This research examined two skill mix staffing models, a mixed registered nurse (RN) and nursing aid model and a 100% RN model, and their impact on patient outcomes. Patient outcomes were pressure ulcers, …

B-Type Natriuretic Peptide (Bnp): A Potential Biomarker For Extubation Failure In Infants Following Cardiac Surgery, Jennifer Flint, Lori Erickson, Dawn Tucker, Erica Molitor-Kirsch

Posters

Background: BNP is a hormone released from the cardiac ventricles in response to increased pressure and volume overload1 and is an important biomarker in heart failure. Following congenital heart surgery, elevated BNP levels correlate with longer duration of mechanical ventilation, low cardiac output syndrome, and increased ICU length of stay2-4 Mechanical ventilation (MV) has an exaggerated impact on cardiopulmonary interactions in children with myocardial dysfunction, and extubation readiness can be difficult to determine post-operatively following congenital heart surgery.

Hypothesis: An increase in post-extubation BNP levels can predict extubation failure and the need for reintubation within 48 hours.

Methods:

Design: prospective, …

Alcohol Exposure Alters Mouse Lung Inflammation In Response To Inhaled Dust., Michael L. Mccaskill, Debra J. Romberger, Jane M. Devasure, Jessica Boten, Joseph H. Sisson, Kristina L. Bailey, Jill A. Poole, Todd A. Wyatt

Journal Articles: Pulmonary & Critical Care Med

Alcohol exposure is associated with increased lung infections and decreased mucociliary clearance. Occupational workers exposed to dusts from concentrated animal feeding operations (CAFOs) are at risk for developing chronic inflammatory lung diseases. Agricultural worker co-exposure to alcohol and organic dust has been established, although little research has been conducted on the combination effects of alcohol and organic dusts on the lung. Previously, we have shown in a mouse model that exposure to hog dust extract (HDE) collected from a CAFO results in the activation of protein kinase C (PKC), elevated lavage fluid cytokines/chemokines including interleukin-6 (IL-6), and the development of …

Non-Typeable Haemophilus Influenzae Decreases Cilia Beating Via Protein Kinase Cε., Kristina L. Bailey, Tricia D. Levan, Daniel A. Yanov, Jacqueline A. Pavlik, Jane M. Devasure, Joseph H. Sisson, Todd A. Wyatt

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Haemophilus influenzae infection of the nasal epithelium has long been associated with observations of decreased nasal ciliary beat frequency (CBF) and injury to the ciliated epithelium. Previously, we have reported that several agents that slow CBF also have the effect of activating protein kinase C epsilon (PKCε) activity in bronchial epithelial cells. The subsequent auto-downregulation of PKCε or the direct inhibition of PKCε leads to the specific detachment of the ciliated cells.

METHODS: Primary cultures of ciliated bovine bronchial epithelial cells were exposed to filtered conditioned media supernatants from non-typeable H. influenzae (NTHi) cultures. CBF and motile points were …

Ventilator Associated Pneumonia Prevention In The Traumatically Injured Patient: Beyond The Bundle!, Cindy Umbrell Msn,Rn,Cns,Ccrn, Kenneth Miller Med, Rrt-Nps

Patient Care Services / Nursing

No abstract provided.

Symptomatic Hypocalcemia During Urinary Alkalinization For Acute Aspirin Toxicity, Jennifer Flint, Bruce Banwart

Posters

A16y/o ingested 165 tablets of 325 mg ASA(1000 mg/kg). He presented to an outside facility 8 hours after ingestion alert with stable vital signs and ASA level 78 mg/dL. Initial lab values showed an arterial blood gas (ABG) pH 7.46, pCO2 26 mmHg, HCO3 18 mmol/L, ionized calcium 1.09 mmol/L, serum calcium 10 mg/dL, albumin 4.5 gm/dL, magnesium 2.1 mg/dL. Urinary alkalinization was initiated with a sodium bicarbonate infusion (NaHCO3) and he arrived to our facility 12 hours after ingestion with Kussmaul respirations and altered mentation. Repeat ASA 116mg/dL, ionized calcium 0.88 mmol/L and serum calcium 8.8 mg/dL. He became …

Cross-Sectional Study Identifying Forms Of Tobacco Used By Shisha Smokers In Pakistan, Sameer-Ur-Rehman, Mohammed Ali Sadiq, Maria Adnan Parekh, Ali Bin Sarwar Zubairi, Philippe. Frossard, Javaid Khan

Section of Otolaryngology, Head & Neck Surgery

Objectives: To estimate the frequency of different forms of tobacco intake such as smoker's tobacco, chewable tobacco and snuff tobacco among shisha smoker's and to study the patterns and predictors of shisha smoking affecting youth from different cities of Pakistan.
Methods: A cross-sectional study was conducted including youth from four cities. Participants were asked to fill out a data collection tool at shisha cafes, shopping malls and restaurants. Data was analyzed using SPSSv.18.
Results: A total of 406 participants, 296 (73%) males and 110 (27%) females were included in the study. There were 163 (40%) cigarette smokers; 65 (16%) chewed …

Examining Fatigue In Copd: Development, Validity And Reliability Of A Modified Version Of Facit-F Scale, Khaled Al-Shair, Hana Muellerova, Janelle Yorke, Stephen I. Rennard, Emiel F.M. Wouters, Nicola A. Hanania, Amir Sharafkhaneh, Jørgen Vestbo, Eclipse Investigators

Journal Articles: Pulmonary & Critical Care Med

INTRODUCTION: Fatigue is a disruptive symptom that inhibits normal functional performance of COPD patients in daily activities. The availability of a short, simple, reliable and valid scale would improve assessment of the characteristics and influence of fatigue in COPD.

METHODS: At baseline, 2107 COPD patients from the ECLIPSE cohort completed the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scale. We used well-structured classic method, the principal components analysis (PCA) and Rasch analysis for structurally examining the 13-item FACIT-F.

RESULTS: Four items were less able to capture fatigue characteristics in COPD and were deleted. PCA was applied to the remaining …

Effects Of Inhaled Corticosteroids On Airway Inflammation In Chronic Obstructive Pulmonary Disease: A Systematic Review And Meta-Analysis, Rachel Jen, Stephen I. Rennard, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the small airways. The effect of inhaled corticosteroids (ICS) on lung inflammation in COPD remains uncertain. We sought to determine the effects of ICS on inflammatory indices in bronchial biopsies and bronchoalveolar lavage fluid of patients with COPD.

METHODS: We searched Medline, Embase, Cinahl, and the Cochrane database for randomized, controlled clinical trials that used bronchial biopsies and bronchoalveolar lavage to evaluate the effects of ICS in stable COPD. For each chosen study, we calculated the mean differences in the concentrations of inflammatory cells before and after treatment …

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 …

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 …