Respiratory System Commons^™

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 …

Effect Of Honey On Anaerobic Performance In Male Collegiate Soccer Players, Katelyn G. Woolfolk

College of Graduate Studies: Theses & Dissertations

Author's abstract: Carbohydrate supplementation has been associated with increased performance in aerobic and anaerobic activity. Honey, specifically, has shown to increase performance in aerobic exercise as well as provide other health benefits. The purpose of this study was to see if honey, a natural substance, has a positive effect on anaerobic performance, rates of perceived exertion, and gastrointestinal distress. Subjects consisted of 18 healthy, Division 1 collegiate male soccer players (19.39 ± 0.85 yr, 75.39 ± 7.97 kg). All had no allergies and were cleared for participation by a certified athletic trainer. Subjects were randomly assigned to one of three …

Successful Use Of A Prolonged Inspiratory Time On The Bunnell Life Pulse Hfjv In Treating Pneumonia Refractory To Conventional And Hfo Ventilation In A Nicu Patient, Kimberly Barner Bs, Rrt-Nps, Laura Monroe Rrt-Nps, Patrick Fitzsimmons Bs, Rrt-Nps

Department of Medicine

No abstract provided.

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 …

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 …

An Evaluation Of The Emerging Interventions Against Respiratory Syncytial Virus (Rsv)-Associated Acute Lower Respiratory Infections In Children, Harish Nair, Vasundhara R. Verma, Evropi Theodoratou, Lina Zgaga, Tanvir Huda, Eric Af Simoes, Peter F. Wright, Igor Rudan, Harry Campbell

Dartmouth Scholarship

Background: Respiratory Syncytial Virus (RSV) is the leading cause of acute lower respiratory infections (ALRI) in children. It is estimated to cause approximately 33.8 million new episodes of ALRI in children annually, 96% of these occurring in developing countries. It is also estimated to result in about 53,000 to 199,000 deaths annually in young children. Currently there are several vaccine and immunoprophylaxis candidates against RSV in the developmental phase targeting active and passive immunization.

Methods: We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed …

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 …

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 …

Genetics Of Sputum Gene Expression In Chronic Obstructive Pulmonary Disease, Weiliang Qiu, Michael H. Cho, John H. Riley, Wayne H. Anderson, Dave Singh, Per Bakke, Amund Gulsvik, Augusto A. Litonjua, David A. Lomas, James D. Crapo, Terri H. Beaty, Bartolome R. Celli, Stephen I. Rennard, Ruth Tal-Singer, Steven M. Fox, Edwin K. Silverman, Craig P. Hersh, Eclipse Investigators

Journal Articles: Pulmonary & Critical Care Med

Previous expression quantitative trait loci (eQTL) studies have performed genetic association studies for gene expression, but most of these studies examined lymphoblastoid cell lines from non-diseased individuals. We examined the genetics of gene expression in a relevant disease tissue from chronic obstructive pulmonary disease (COPD) patients to identify functional effects of known susceptibility genes and to find novel disease genes. By combining gene expression profiling on induced sputum samples from 131 COPD cases from the ECLIPSE Study with genomewide single nucleotide polymorphism (SNP) data, we found 4315 significant cis-eQTL SNP-probe set associations (3309 unique SNPs). The 3309 SNPs were tested …

Cerebral Salt Wasting Syndrome In Tuberculous Meningitis, Abdul Jabbar, Syed Nadir Farrukh, Rabbia Khan

Section of Internal Medicine

Case of a seventy year old female, who developed cerebral salt wasting syndrome in association with Tuberculous Meningitis is presented.

Crystal Structure Of The Cystic Fibrosis Transmembrane Conductance Regulator Inhibitory Factor Cif Reveals Novel Active-Site Features Of An Epoxide Hydrolase Virulence Factor, Christopher D. Bahl, Christophe Morisseau, Jennifer M. Bomberger, Bruce A. Stanton, Bruce D. Hammock, George A. O'Toole, Dean R. Madden

Dartmouth Scholarship

Cystic fibrosis transmembrane conductance regulator (CFTR) inhibitory factor (Cif) is a virulence factor secreted by Pseudomonas aeruginosa that reduces the quantity of CFTR in the apical membrane of human airway epithelial cells. Initial sequence analysis suggested that Cif is an epoxide hydrolase (EH), but its sequence violates two strictly conserved EH motifs and also is compatible with other alpha/beta hydrolase family members with diverse substrate specificities. To investigate the mechanistic basis of Cif activity, we have determined its structure at 1.8-A resolution by X-ray crystallography. The catalytic triad consists of residues Asp129, His297, and Glu153, which are conserved across the …

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 % …

Variables Predictive Of Outcome In Patients With Acute Hypercapneic Respiratory Failure Treated With Noninvasive Ventilatio, Nawal Salahuddin, Muhammad Irfan, Shereen Khan, Muhammad Naeem, Ahmad Suleman Haque, Shahid Javed Husain, Nisar Ahmed Rao, Ali Bin Sarwar Zubairi, Javaid Khan

Section of Pulmonary & Critical Care

OBJECTIVE: To assess results with NIV in acute hypercapneic respiratory failure and to identify outcome predictors.

METHODS: This was a retrospective observational study on consecutive patients presenting with acute type II respiratory failure and meeting criteria for NIV use over a 5 year period. Patients presenting with haemodynamic instability, inability to protect their airway, malignant arrhythmias and recent oesophageal surgery were excluded. Univariate and Multivariate regression analysis was used to determine the impact on survival. A p value of < 0.05 was considered statistically significant. Software used was SPSS 14.

RESULTS: Total numbers of patients included were 119; 52.9% were males. Mean age was 63.4 +/- 11.9 years. Overall Survival to …

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 …