Critical Care Commons^™

2014 Massachusetts Family Impact Seminar: A Lot On Our Plate; Chronic Health Threats In Massachusetts, Ira S. Ockene M.D., Christina D. Economos Ph.D, Barbara Goldoftas Ph.D, Denise A. Hines Ph.D., Caitlin Alcorn, Jacqueline A. Daigneault, Jordan R. Daley, Maura A. Flanagan, Carsten-Hendrik Rasche, Heather Rios, Julia Tran, Liam Kelly Fleming

Mosakowski Institute for Public Enterprise

A Lot on Our Plate: Chronic Health Threats in Massachusetts is the fifth Massachusetts Family Impact Seminar, and is designed to emphasize a family perspective in policymaking on issues related to childhood obesity, cardiovascular disease, and type 2 diabetes. In general, Family Impact Seminars analyze the consequences an issue, policy, or program may have for families.

Ready-Set-Go! A Clinical Practice Guideline That Promotes Safe Care Of The Sedated Patient Before, During And After Transport, Kimberly A. Martin Rn, Cnrn, Jennifer Houp Rn, Cnrn

Patient Care Services / Nursing

No abstract provided.

What Happens To Patients With Copd With Long-Term Oxygen Treatment Who Receive Mechanical Ventilation For Copd Exacerbation? A 1-Year Retrospective Follow-Up Study, N. Hajizadeh, K. Goldfeld, K. Crothers

Journal Articles

We performed a retrospective cohort study of patients with chronic obstructive lung disease (COPD) on long-term oxygen treatment (LTOT) who received invasive mechanical ventilation for COPD exacerbation. Of the 4791 patients, 23% died in the hospital, and 45% died in the subsequent 12 months. 67% of patients were readmitted at least once in the subsequent 12 months, and 26.8% were discharged to a nursing home or skilled nursing facility within 30 days. We conclude that these patients have high mortality rates, both in-hospital and in the 12 months postdischarge. If patients survive, many will be readmitted to the hospital and …

Depression In Pulmonary Arterial Hypertension And Interstitial Lung Diseases, S. Verma, J. Cardenas-Garcia, P. R. Mohapatra, A. Talwar

Journal Articles

Advanced lung diseases such as pulmonary arterial hypertension (PAH) and interstitial lung diseases (ILD) are chronic diseases that cause significantly high morbidity and mortality. As a result, patients can undergo some psychological changes leading to a poor quality of life and depression. Diagnosis of depression is often obscured because fatigue and apathy, two common symptoms of depression, frequently overlap with PAH and ILD. Healthcare providers are sometimes reluctant to ask or mistakenly believe that these symptoms are part of the ongoing disease process, rather than a serious condition like depression. Screening tools are available for physicians to be well positioned …

Effects Of Pulmonary Rehabilitation On Fatigue Severity Scale In Patients With Lung Disease, A. Talwar, S. Sahni, S. John, S. Verma, J. Cardenas-Garcia, N. Kohn

Journal Articles

INTRODUCTION: Fatigue is a known symptom of advanced lung disease and impacts quality of life and psychological health. Many of these patients undergo pulmonary rehabilitation as part of their therapy. Understanding the effect of pulmonary rehabilitation on fatigue in these patients is important, as one may be able to design more focused rehabilitation programs. The aim of this study is to evaluate the effect of pulmonary rehabilitation on fatigue as measured by the Fatigue Severity Scale (FSS) in patients with advanced lung disease. MATERIAL AND METHODS: Patients were enrolled in a standardized 6 week pulmonary rehabilitation program. They were asked …

An Obligatory Role Of Nf-Kappa B In Mediating Bone Marrow Derived Endothelial Progenitor Cell Recruitment And Proliferation Following Endotoxemic Multiple Organ Injury In Mice, S. Z. Mao, X. B. Ye, G. Liu, D. M. Song, S. F. Liu

Journal Articles

Background: Recruitment of bone marrow derived endothelial progenitor cells (BMDEPCs) alleviates multiple organ injury (MOI) and improves outcomes. However, mechanisms mediating BMDEPC recruitment following septic MOI remain largely unknown. This study characterized the kinetics of BMDEPC recruitment and proliferation and defined the role of NF-kappa B in regulating BMDEPC recruitment and proliferation. Methods and Main Findings: Chimeric mice with an intact or disrupted NF-kappa B p50 gene and BMDEPC-restricted expression of green fluorescent protein were created and injected with LPS (2 mg/kg, i.p.). BMDEPC recruitment and proliferation in multiple organs were quantified. BMDEPC recruitment and proliferation are highly organ-dependent. Lungs …

Resolution Of Severe Obstructive Sleep Apnea After Treatment Of Anti-Muscle Kinase Receptor-Positive Myasthenia Gravis Despite 60-Pound Weight Gain, M. Morgenstern, E. Singas, B. Zleik, H. Greenberg

Journal Articles

Obstructive sleep apnea (OSA) in patients with myasthenia gravis (MG) may be caused by reduced pharyngeal dilator muscle activity. We report a patient with anti-muscle kinase receptor MG with severe OSA and hypoventilation that resolved upon successful treatment of MG despite a 60-lb weight gain.

Efficacy Of Nasal Mometasone For The Treatment Of Chronic Sinonasal Disease In Patients With Inadequately Controlled Asthma, A. E. Dixon, M. Castro, R. I. Cohen, L. B. Gerald, J. T. Holbrook, C. G. Irvin, S. Mohapatra, S. P. Peters, S. Rayapudi, E. A. Sugar, R. A. Wise

Journal Articles

BACKGROUND: Chronic sinonasal disease is common in asthmatic patients and associated with poor asthma control; however, there are no long-term trials addressing whether chronic treatment of sinonasal disease improves asthma control. OBJECTIVE: We sought to determine whether treatment of chronic sinonasal disease with nasal corticosteroids improves asthma control, as measured by the Childhood Asthma Control Test and Asthma Control Test in children and adults, respectively. METHODS: A 24-week multicenter, randomized, placebo-controlled, double-blind trial of placebo versus nasal mometasone in adults and children with inadequately controlled asthma was performed. Treatments were randomly assigned, with concealment of allocation. RESULTS: Two hundred thirty-seven …

Ulinastatin Activates Haem Oxygenase 1 Antioxidant Pathway And Attenuates Allergic Inflammation, D. M. Song, G. Song, Y. H. Niu, W. Song, J. T. Wang, L. Yu, J. W. Yang, H. Steinberg, S. F. Liu, B. S. Wang, +1 Additional Author

Journal Articles

Background and PurposeUlinastatin (UTI), a serine protease inhibitor, was recently found to have an anti-inflammatory action. However, the mechanisms mediating this anti-inflammatory effect are not well understood. This study tested the hypothesis that UTI suppresses allergic inflammation by inducing the expression of haem oxygenase 1 (HO1). Experimental ApproachControl mice and mice sensitized (on days 1, 9 and 14) and challenged (on days 21 to 27) with ovalbumin (OVA) were treated with UTI. The effects of UTI on basal expression of HO1 and that induced by OVA challenge were examined. The involvement of UTI-induced HO1 expression in anti-inflammatory and antioxidant effects …

Non-Emphysematous Chronic Obstructive Pulmonary Disease Is Associated With Diabetes Mellitus, Craig P. Hersh, Barry J. Make, David A. Lynch, R. Graham Barr, Russell P. Bowler, Peter M.A. Calverley, Peter J. Castaldi, Michael H. Cho, Harvey O. Coxson, Dawn L. Demeo, Marilyn G. Foreman, Meilan K. Han, Benjamin J. Harshfield, John E. Hokanson, Sharon Lutz, Joe W. Ramsdell, Elizabeth A. Regan, Stephen I. Rennard, Joyce D. Schroeder, Frank C. Sciurba, Robert M. Steiner, Ruth Tal-Singer, Edwin Van Beek, Edwin K. Silverman, James D. Crapo, Copdgene And Eclipse Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been classically divided into blue bloaters and pink puffers. The utility of these clinical subtypes is unclear. However, the broader distinction between airway-predominant and emphysema-predominant COPD may be clinically relevant. The objective was to define clinical features of emphysema-predominant and non-emphysematous COPD patients.

METHODS: Current and former smokers from the Genetic Epidemiology of COPD Study (COPDGene) had chest computed tomography (CT) scans with quantitative image analysis. Emphysema-predominant COPD was defined by low attenuation area at -950 Hounsfield Units (LAA-950) ≥10%. Non-emphysematous COPD was defined by airflow obstruction with minimal to no emphysema (LAA-950 …

Sexually-Dimorphic Targeting Of Functionally-Related Genes In Copd, Kimberly Glass, John Quackenbush, Edwin K. Silverman, Bartolome Celli, Stephen I. Rennard, Guo-Cheng Yuan, Dawn L. Demeo

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: There is growing evidence that many diseases develop, progress, and respond to therapy differently in men and women. This variability may manifest as a result of sex-specific structures in gene regulatory networks that influence how those networks operate. However, there are few methods to identify and characterize differences in network structure, slowing progress in understanding mechanisms driving sexual dimorphism.

RESULTS: Here we apply an integrative network inference method, PANDA (Passing Attributes between Networks for Data Assimilation), to model sex-specific networks in blood and sputum samples from subjects with Chronic Obstructive Pulmonary Disease (COPD). We used a jack-knifing approach to …

The Association Of Plasma Biomarkers With Computed Tomography-Assessed Emphysema Phenotypes, Brendan J. Carolan, Grant Hughes, Jarrett Morrow, Craig P. Hersh, Wanda K. O'Neal, Stephen I. Rennard, Sreekumar G. Pillai, Paula Belloni, Debra A. Cockayne, Alejandro P. Comellas, Meilan Han, Rachel L. Zemans, Katerina Kechris, Russell P. Bowler

Journal Articles: Pulmonary & Critical Care Med

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a phenotypically heterogeneous disease. In COPD, the presence of emphysema is associated with increased mortality and risk of lung cancer. High resolution computed tomography (HRCT) scans are useful in quantifying emphysema but are associated with radiation exposure and high incidence of false positive findings (i.e., nodules). Using a comprehensive biomarker panel, we sought to determine if there was a peripheral blood biomarker signature of emphysema.

METHODS: 114 plasma biomarkers were measured using a custom assay in 588 individuals enrolled in the COPDGene study. Quantitative emphysema measurements included percent low lung attenuation (%LAA) ≤ …

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, …