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Christine de la Loge, MSc1 Béatrice Tugaut, MSc1 Fatoumata Fofana, MSc1 Jérémy Lambert, PhD1 Michael Hennig, PhD2 Uta Tschiesner, MD3 Mitra Vahdati-Bolouri, MRCP, MFPM4 Afisi Segun Ismaila, PhD5 Yogesh Suresh Punekar, PhD6
Author Affiliations
- Mapi, Patient-Centered Outcomes, Lyon, France
- Biostatistics and Epidemiology, GlaxoSmithKline, Munich, Germany
- Former employee of GlaxoSmithKline, Munich, Germany
- Research and Development, Global Respiratory Franchise, GlaxoSmithKline, Brentford, United Kingdom
- Value Evidence and Outcomes, GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina; Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
- Value Evidence and Outcomes, GlaxoSmithKline, Brentford, United Kingdom
Address correspondence to:
Yogesh Suresh Punekar, PhD
GlaxoSmithKline
Brentford, TW8 9GS, UK
Email: yogesh.q.punekar@gsk.com
Phone: +44 (0) 208 047 4264
Abstract
Background: This meta-analysis assessed the relationship between change from baseline (CFB) in spirometric measurements (trough forced expiratory volume in 1 second [FEV1] and FEV1 area under the curve [AUC]) and patient-reported outcomes (St. George’s Respiratory Questionnaire total score [SGRQ] CFB, Transition Dyspnea Index [TDI] and exacerbation rates) after 6-12 months’ follow-up, using study treatment-group level data.
Methods: A systematic literature search was performed for randomized controlled trials of ≥24 weeks duration in adults with chronic obstructive pulmonary disease (COPD). Studies reporting ≥1 spirometric measurement and ≥1 patient-reported outcome (PRO) at baseline and at study endpoint were selected. The relationships between PROs and spirometric endpoints were assessed using Pearson correlation coefficient and meta-regression.
Results: Fifty-two studies (62,385 patients) were included. Primary weighted analysis conducted at the last assessment showed a large significant negative correlation (r, −0.68 [95% confidence interval (CI); −0.77, −0.57]) between trough FEV1 and SGRQ. Improvement of 100 mL in trough FEV1 corresponded to a 5.9 point reduction in SGRQ. Similarly, a reduction of 4 points on SGRQ corresponded to 40 mL improvement in trough FEV1 (p<0.001). The weighted correlation coefficients of trough FEV1 with TDI, exacerbation rate (all) and exacerbation rate (moderate/severe) at last assessment point were 0.57, -0.69 and -0.57, respectively (all p<0.05). For the analyses excluding placebo groups, the correlations of FEV1 with SGRQ and TDI were lower but significant.
Conclusions: A strong association exists between changes in spirometric measurements and changes in PROs.
Citation
Citation: de la Loge C, Tugaut B, Fofana F, et al. Relationship between FEV1 and patient-reported outcomes changes: Results of a meta-analysis of randomized trials in stable COPD. Chronic Obstr Pulm Dis (Miami). 2016; 3(2): 519-538. doi: http://dx.doi.org/10.15326/jcopdf.3.2.2015.0152
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Suchit D. Kumbhare, MBBS, MSCR1 Tatsiana Beiko, MD1 Susan R. Wilcox, MD1,2 Charlie Strange, MD1
Author Affiliations
- Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, Medical University of South Carolina, Charleston
- Division of Emergency Medicine, Department of Medicine, Medical University of South Carolina, Charleston
Address correspondence to:
Charlie Strange, MD
Division of Pulmonary and Critical Care Medicine
Medical University of South Carolina
96 Jonathan Lucas St. 812 CSB
Charleston, SC, 29425
Phone: 843-792-3174
strangec@musc.edu
Abstract
Rationale: Several chronic obstructive pulmonary disease (COPD) studies have evaluated risk factors for emergency department (ED) visits or hospitalizations, and found insufficient data available about social and demographic factors that drive these behaviors. This U.S. study was designed to describe the characteristics of COPD patients with ED visits or a hospitalization and to investigate how often common COPD comorbidities are present in these individuals.
Methods: Data for 7180 COPD patients regarding demographic factors, comorbidities, smoking status, and ED visits or hospitalization was obtained from the 2012 Behavioral Risk Factor Surveillance System (BRFSS) survey. Logistic regression analysis was used to adjust demographic factors and smoking status to model the correlation between patients with ED visits or hospitalizations and morbidities generating odds ratios (OR) and confidence intervals (CI).
Results: Among diagnosed COPD patients in the BRFSS, 16.5% had ED visits or hospitalization in the previous year. These individuals were younger, had a lower socio-economic status (lower education, lower income, and more often unemployed) and 23.4% of the individuals could not visit a doctor because of the financial difficulties compared to 16.7% who had no visit (p<0.0001 for all comparisons). The prevalence of comorbidities was higher in those with ED visits or hospitalization compared to those without.
Conclusion: In a population representative of COPD patients, lower socio-economic status and higher comorbidities are associated with ED visits or hospitalization. Studies are needed to further elucidate the complex relationship between COPD, comorbidities, and ED visits or hospitalization.
Citation
Citation:Kumbhare SD, Beiko T, Wilcox SR, Strange C. Characteristics of COPD patients using United States emergency care or hospitalization. Chronic Obstr Pulm Dis (Miami). 2016; 3(2): 539-548. doi: http://dx.doi.org/10.15326/jcopdf.3.2.2015.0155
Keywords
COPD, comorbidity, hospitalization, emergency department, BMI, Behavioral Risk Factor Surveillance System, prevalence, ED, emergency room, ER, body mass index, BRFSS
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Edward Kerwin, MD1 Thomas M. Siler, MD2 Phillip Korenblat, MD3 Alexander White, MD4 Joerg H. Eckert, PhD5 Michelle Henley, MSc6 Francesco Patalano, MD5 Peter D’Andrea, MD6
Author Affiliations
- Clinical Research Institute of Southern Oregon, Medford
- Midwest Chest Consultants, St. Charles, Missouri
- The Clinical Research Center, St. Louis, Missouri
- Progressive Medical Research, Port Orange, Florida
- Novartis Pharma AG, Basel, Switzerland
- Novartis Pharmaceuticals Corporation, East Hanover, New Jersey
Address correspondence to:
Edward Kerwin, MD
Clinical Research Institute of Southern Oregon
3860 Crater Lake Avenue
Medford, OR 97504
Phone: 541-858-1003
Email: ekerwin@criresearch.com
Abstract
Long-acting bronchodilators including muscarinic antagonists are central to the management of patients with COPD. The Glycopyrrolate Effect on syMptoms and lung function (GEM2) study assessed the efficacy and safety of twice-daily glycopyrrolate 15.6 μg in patients with moderate-to-severe airflow limitation.
This 12-week multicenter, double-blind study randomized (1:1) patients to glycopyrrolate 15.6 μg twice daily (b.i.d.) or placebo both delivered via the NeohalerTM device. The primary objective was superiority of glycopyrrolate compared with placebo for forced expiratory volume in 1 second (FEV1) standardized area under curve (AUC) between 0 and 12 hours post dosing (FEV1 AUC0-12h) at week 12. Other outcomes included additional spirometry parameters, health status using St George’s Respiratory Questionnaire (SGRQ), dyspnea via Transition Dyspnea Index (TDI), rescue medication use and COPD symptoms reported by patients via the electronic diary. Safety was also assessed.
Of the 432 patients randomized (glycopyrrolate, n=216; placebo, n=216), 96% completed the planned treatment phase. The study met its primary objective (superiority of glycopyrrolate compared with placebo for FEV1 AUC0-12h). Compared with placebo, glycopyrrolate showed significant improvements in lung function parameters (p<0.001). Health status (SGRQ total score and COPD assessment test), rescue medication use and daily total COPD symptom scores were significantly improved with glycopyrrolate versus placebo over 12 weeks. Improvements in dyspnea were observed with glycopyrrolate and placebo although the treatment difference was not statistically significant. Overall, differences in the incidences of adverse events and serious adverse events between the groups were not considered clinically meaningful. No deaths were reported.
Twice-daily glycopyrrolate 15.6 μg showed statistically significant and clinically meaningful improvements compared with placebo in lung function, COPD symptoms, health status, and rescue medication usage in COPD patients with moderate-to-severe airflow limitation.
Clinical Trial Registration: NCT01715298
Citation
Citation: Kerwin E, Siler TM, Korenblat P, et al. Efficacy and safety of twice-daily glycopyrrolate versus placebo in patients with COPD: the GEM2 study. Chronic Obstr Pulm Dis (Miami). 2016; 3(2): 549-559. doi: http://dx.doi.org/10.15326/jcopdf.3.2.2015.0157
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Sara Ongay, PhD1 Marijke Sikma1,2 Peter Horvatovich, PhD1 Jos Hermans1 Bruce E. Miller, MD, PhD4 Nick H.T. ten Hacken, MD, PhD3 Rainer Bischoff, PhD1
Author Affiliations
- University of Groningen, Department of Pharmacy, Analytical Biochemistry, Groningen, The Netherlands
- Van Hall Larenstein Hogeschool, Leeuwarden, Agora, The Netherlands
- University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- GlaxoSmithKline Research and Development, King of Prussia, Pennsylvania
Address correspondence to:
Rainer Bischoff, PhD
Phone: +31-50-363-3338 (secr. 3336),
Fax +31-50-363-7582,
Email: r.p.h.bischoff@rug.nl.
Abstract
Background: Desmosine (DES) and isodesmosine (IDES) have been widely discussed as potential biomarkers of COPD. However, their clinical utility and validity remains unproven.
Aim: This study aims to progress DES/IDES evaluation as a chronic obstructive pulmonary disease (COPD) biomarker by investigating its urinary excretion in a large sample cohort with respect to a) which factors influence DES/IDES levels in a population of healthy control individuals and COPD individuals; b) whether DES/IDES levels enable the differentiation between COPD individuals and healthy control individuals; c) whether DES/IDES can be used to differentiate between fast and slow decliners in lung function.
Methods: Urinary DES and IDES were quantified in 365 individuals (147 healthy control individuals and 218 COPD individuals) from the Evaluation of COPD Longitudinally to Indentify Predictive Surrogate Endpoints (ECLIPSE) study (NCT00292552) by employing a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method.
Results: Age, gender, body mass index (BMI) and smoking have a significant (p<0.05) influence on DES/IDES urinary excretion and need to be corrected for when investigating DES/IDES as a disease biomarker. Urinary DES/IDES allowed a statistically relevant differentiation (p<0.05) between stable COPD individuals and healthy control individuals, however, assay sensitivity and specificity were low (62% and 73%, respectively). Furthermore, urinary DES/IDES does not allow the differentiation of fast and slow decliners in lung function.
Conclusions: The present results suggest that while urinary DES/IDES excretion is related to COPD, it is not a sensitive or specific biomarker for COPD diagnosis or prognosis.
Citation
Citation: Ongay S, Sikma M, Horvatovich P, et al. Free urinary desmosine and isodesmosine as COPD biomarkers: The relevance of confounding factors. Chronic Obstr Pulm Dis (Miami). 2016; 3(2): 560-569. doi: http://dx.doi.org/10.15326/jcopdf.3.2.2015.0159
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Cynthia Kim, MD1* Wei Ouyang, MD2* Chandra Dass, MD2 Huaqing Zhao, PhD3 Gerard J. Criner, MD1 and the COPDGene Investigators
Author Affiliations
- Department of Pulmonary and Critical Care Medicine, Temple University Hospital, Philadelphia, Pennsylvania
- Department of Radiology, Temple University Hospital, Philadelphia, Pennsylvania
- Temple Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania
*Co-first Authors
Address correspondence to:
Cynthia Kim, MD
Temple Lung Center
7th Floor Parkinson Pavilion
3401 North Broad Street
Philadelphia, PA 19140
Phone: 267-858-2735
Email: cynthia.kim@tuhs.temple.edu
Abstract
Background: Gastroesophageal reflux disease (GERD) is associated with frequent chronic obstructive pulmonary disease (COPD) exacerbations. Hiatal hernia (HH) contributes to GERD pathogenesis and is identifiable on chest high-resolution computed tomography (HRCT). We hypothesize that the presence of an HH on HRCT identifies those at increased risk for acute exacerbation of COPD.
Methods: We retrospectively reviewed a prospectively enrolled cohort of smokers with and without airflow obstruction. HHs were identified visually on inspiratory HRCT. Individuals’ demographic and clinical information was compared with secondary analysis performed using a propensity score generated matched cohort.
Results: There were 523 COPD individuals and 607 unobstructed smokers. COPD individuals had more HHs than unobstructed smokers, (11.6% versus 6.1%, p < 0.001). COPD individuals with hernias were older, female, overweight and GERD positive as compared to those without hernia. There was no difference in self-reported exacerbation rates or hospitalizations per year, but similar severity of obstruction, smoking rates and long-term oxygen use. Analysis with the matched cohort revealed no significant difference in exacerbation rates.
Conclusions: Presence of HHs on inspiratory HRCT scan did not predict worse symptoms or exacerbation rate in COPD individuals. Those with HHs were older, more obese, and predominantly female compared to those without HHs.
Citation
Citation: Kim C, Ouyang W, Dass C, Zhao H, Criner GJ, COPDGene Investigators. Hiatal hernia on chest high-resolution computed tomography and exacerbation rates in COPD individuals. Chronic Obstr Pulm Dis (Miami). 2016; 3(2): 570-579. doi: http://dx.doi.org/10.15326/jcopdf.3.2.2015.0158
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Diego Bonilla Arcos, MD1 Jerry A. Krishnan, MD, PhD2 R. William Vandivier, MD3 Jonathan E. Sevransky, MD, MHS4 William Checkley, MD, PhD5 Tyree H. Kiser, PharmD6 Jamie L. Sullivan, MPH7 John W. Walsh,7 Robert A. Wise, MD5 and Kevin C. Wilson, MD1,8 for the DECIDE9 Investigators
Author Affiliations
- The Pulmonary Center, Boston University School of Medicine, Massachusetts
- University of Illinois Hospital & Health Sciences System, Chicago
- Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver Anschutz Medical Campus, Denver
- Division of Pulmonary and Critical Care Medicine, Emory University, Atlanta, Georgia
- Division of Pulmonary and Critical Care, School of Medicine, Johns Hopkins University, Baltimore, Maryland
- Department of Clinical Pharmacy, University of Colorado Denver Anschutz Medical Campus, Denver
- COPD Foundation, Washington, D.C.
- Documents and Patient Education Department, American Thoracic Society, New York, New York
- DosE of CorticosteroIDs for Exacerbations of COPD (DECIDE)
Address correspondence to:
Kevin C. Wilson, M.D.
The Pulmonary Center
72 E. Concord Street, R-304
Boston, MA 02118
Email: kcwilson@bu.edu
Abstract
Background: Treatment of an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with systemic steroids reduces treatment failure, shortens hospital length of stay, improves lung function, and reduces dyspnea. However, it can also cause hyperglycemia, delirium, fluid retention, and other side effects. The balance of these desirable and undesirable effects probably varies according to the steroid dose.
Methods: We asked the question, “Should patients having an AECOPD receive low-dose or high-dose systemic steroids?” We searched Medline and the Cochran Central Register of Controlled Trials (CENTRAL) using a sensitive search strategy built around the medical subject heading, “COPD,” and variations of the keywords exacerbation, steroids, and randomized trials. Our search yielded 1702 articles in Medline and 885 articles in CENTRAL; we reviewed the full text of 35 articles and selected 11 studies that met the following conditions: randomized trial, enrolled patients having an AECOPD, compared one systemic steroid regimen to another, measured clinical outcomes, and was published in a peer-reviewed journal.
Results: None of the selected trials directly compared the effects of different systemic steroid doses on clinical outcomes in patients with AECOPD. Four trials compared durations of steroid treatment, 3 trials compared types of steroids, 1 trial compared routes of steroid delivery, and 3 trials compared multiple variables.
Conclusion: There is a paucity of data to support the selection of a systemic steroid dose in patients having an AECOPD. Randomized trials that measure patient-centered outcomes and compare doses of systemic steroids in patients having an AECOPD are needed.
Citation
Citation: Arcos DB, Krishnan JA, William KR, et al. High-dose versus low-dose systemic steroids in the treatment of acute exacerbations of chronic obstructive pulmonary disease: A systematic review. Chronic Obstr Pulm Dis (Miami). 2016; 3(2): 580-588. doi: http://dx.doi.org/10.15326/jcopdf.3.2.2015.0178
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