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Robert A. Wise, MD1 Russell A. Acevedo, MD2 Antonio R. Anzueto, MD3 Nicola A. Hanania, MD, MS4 Fernando J. Martinez, MD5 Jill A. Ohar, MD6 Donald P. Tashkin, MD7
Author Affiliations
- Johns Hopkins University School of Medicine, Baltimore, Maryland
- Crouse Hospital, Syracuse, New York
- University of Texas Health Science Center, and South Texas Veterans Health Care System, San Antonio, Texas
- Section of Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, Texas
- Weill Cornell Medical College, New York, New York
- Wake Forest Baptist Medical Center, Winston-Salem, North Carolina
- David Geffen School of Medicine at the University of California, Los Angeles
Address correspondence to:
Robert A. Wise, MD
Email: rwise@jhmi.edu
Phone: (410)550-0545
Abstract
Determining which patients with COPD may benefit from a nebulized long-acting beta2-agonist (LABA) is a challenge in current practice. In the absence of strong clinical guidelines addressing this issue, an expert panel convened to develop guiding principles for the use of nebulized LABA therapy in patients with COPD. This article summarizes these guiding principles and other practical issues discussed during a roundtable meeting.
Citation
Citation: Wise RA, Acevedo RA, Anzueto AR, et al. Guiding principles for the use of nebulized long-acting beta2-agonists in patients with COPD: An expert panel consensus. Chronic Obstr Pulm Dis (Miami). 2017; 4(1): 7-20. doi: http://doi.org/10.15326/jcopdf.4.1.2016.0141
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Sanjay Sethi, MD1 Charles Fogarty, MD2 Nicola A. Hanania, MD3 Fernando J. Martinez, MD, MS4 Stephen Rennard, MD5 Chad Orevillo, MPH6 Patrick Darken, PhD7 Earl St. Rose, MS, MBA8 Shannon Strom, PhD9 Tracy Fischer, PharmD9 Michael Golden9 Sarvajna Dwivedi, PhD10 Colin Reisner, MD 6
Author Affiliations
- Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo
- Spartanburg Medical Research, Spartanburg, South Carolina
- Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, Texas
- Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, New York
- Clinical Discovery Unit, AstraZeneca, Cambridge, Cambridgeshire, United Kingdom
- Clinical Development, Pearl Therapeutics Inc., Morristown, New Jersey
- Biostatistics, Pearl Therapeutics Inc., Morristown, New Jersey
- Clinical Operations, Pearl Therapeutics Inc., Morristown, New Jersey
- Regulatory Affairs, Pearl Therapeutics Inc., Durham, North Carolina
- Pearl Therapeutics Inc., Redwood City, California
Address correspondence to:
Sanjay Sethi, MD
Phone: 001 716 862 7875
Email: ssethi@buffalo.edu
Abstract
Background: Co-Suspension™ Delivery Technology offers a novel pharmaceutical platform for inhaled drug therapy. This randomized, double-blind, placebo-controlled, single-dose study (NCT01349868) evaluated the efficacy of a range of doses for formoterol fumarate (FF) delivered using Co-Suspension delivery technology via a pressurized metered dose inhaler (MDI) versus placebo in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). Secondary objectives included determination of non-inferior efficacy and systemic exposure compared with open-label Foradil® 12 μg (Foradil® Aerolizer®; formoterol fumarate dry powder inhaler).
Methods: Patients received each of the 6 study treatments (FF MDI [7.2, 9.6 and 19.2μg], placebo MDI and open-label Foradil® [12 and 24µg]), separated by 3–10 days. Spirometry was performed 60 and 30 minutes prior to and at regular intervals up to 12 hours post-administration of study drug. The primary outcome measure was the change in forced expiratory volume in 1 second (FEV1) area under the curve between 0 and 12 hours (AUC0-12) relative to test day baseline.
Results: A total of 50 patients were randomized to study treatment sequences. All doses of FF MDI demonstrated superiority to placebo (p<0.0001) and non-inferiority to Foradil® 12μg, on bronchodilator outcome measures. No serious adverse events were reported during the study.
Conclusions: This study demonstrates non-inferiority of bronchodilator response and bioequivalent exposure of FF MDI 9.6μg to Foradil® 12μg, with both agents exhibiting a similar safety profile in patients with moderate-to-severe COPD. This study supports the selection of FF MDI 9.6µg for further evaluation in Phase III trials.
Citation
Citation: Sethi S, Fogarty C, Hanania NA, et al. Efficacy of formoterol fumarate delivered by metered dose inhaler using Co-suspension™ delivery technology versus Foradil® aerolizer® in moderate-to-severe COPD: a randomized, dose-ranging study. Chronic Obstr Pulm Dis (Miami). 2017; 4(1): 21-33. doi: http://doi.org/10.15326/jcopdf.4.1.2016.0158
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Shuren Ma, PhD1 Yong Y. Lin, PhD1 Jerome O. Cantor, MD1 Kenneth R. Chapman, MD2 Robert A. Sandhaus, MD3 Michael Fries, PhD4 Jonathan M. Edelman, MD4 N. Gerard McElvaney, MD5 Gerard M. Turino, MD1
Author Affiliations
- James P. Mara Center for Lung Disease at Mt. Sinai, Department of Medicine, St. Luke’s-Roosevelt Hospital, New York, New York
- Asthma and Airway Centre, University Health Network, Toronto Western Hospital, Toronto, Ontario, Canada
- Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colorado
- Clinical Strategy and Development, CSL Behring, King of Prussia, Pennsylvania
- Department of Respiratory Medicine, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin, Ireland
Address correspondence to:
Gerard M. Turino, MD
Professor of Medicine
Division of Pulmonary, Critical Care and Sleep Medicine
Mount Sinai Roosevelt and Mount Sinai St. Luke's,
New York, NY
Phone: (212) 523-5919 / (212) 523-8672
Email: gmt1@columbia.edu
Abstract
The RAPID (NCT00261833; N=180) and RAPID Extension (NCT00670007; N=140) trials demonstrated significantly reduced lung density decline in patients with alpha-1 antitrypsin deficiency (AATD) receiving alpha-1 proteinase inhibitor (A1PI) versus placebo. Desmosine and isodesmosine (DES/IDES) are unique crosslinkers of mature elastin fibers and are utilized as measures of elastin degradation. The aim of this post-hoc study was to determine the effect of A1PI therapy on DES/IDES levels in patients from RAPID/RAPID Extension.
Plasma levels of DES/IDES were measured using high-performance liquid chromatography and tandem mass spectrometry. Correlation between changes in DES/IDES levels and computed tomography (CT) lung density decline was assessed.
Analysis showed that DES/IDES levels were significantly reduced versus baseline in patients receiving A1PI at all time points, from month 3 through month 48. A significant increase from baseline in DES/IDES was observed with placebo at month 24 (n=54; 0.016; p=0.018). DES/IDES change from baseline was significantly different with A1PI versus placebo at months 3 (-0.021; 95% confidence interval [CI] -0.037, 0.004; p=0.026), 12 (-0.040; 95% CI -0.055, 0.025; p<0.001), and 24 (-0.052; 95% CI -0.070, 0.034; p<0.001). Placebo patients started A1PI therapy at month 24 and showed significant reductions in plasma DES/IDES at months 36 (p<0.001) and 48 (p<0.001). Reduced elastin degradation was associated with slower lung density decline (p=0.005), correlating a chemical index of therapy with an anatomical index by CT.
In conclusion, A1PI therapy reduced elastin degradation, including pulmonary elastin, in patients with AATD. These data support using DES/IDES levels as biomarkers to monitor emphysema progression and treatment response.
Citation
Citation: Ma S, Lin YY, Cantor JO, et al. The effect of alpha-1 proteinase inhibitor on biomarkers of elastin degradation in alpha-1 antitrypsin deficiency: An analysis of the RAPID/RAPID Extension trials. Chronic Obstr Pulm Dis (Miami). 2017; 4(1): 34-44. doi: http://doi.org/10.15326/jcopdf.4.1.2016.0156
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Katherine A. Safka, MD, FRCP(C)1 Joshua Wald, MD, FRCP(C)1 Hongyu Wang, MD, PhD1 Luke McIvor,1 Andrew McIvor, MD, MSc, FRCP(C)1
Author Affiliations
- Firestone Institute for Respiratory Health, McMaster University, Hamilton, Ontario, Canada
Address correspondence to:
R.A. McIvor, MD
T2127 FIRH, St. Joseph’s Healthcare
50 Charlton Avenue East
McMaster University
Hamilton, Ontario, Canada
Email: amcivor@stjosham.on.ca
Phone: (905)522-1155 Ext 34330
Abstract
Background and Objective: The Global initiative for chronic Obstructive Lung Disease (GOLD) guidelines recommend using a combination of spirometry, symptoms and exacerbation history to classify patients into 4 categories (A, B, C, D) to guide treatment decisions along with a stepwise increase in therapy. Our objectives were to identify the GOLD stage of patients in respiratory outpatient clinics and assess how treatment compares to guideline recommendations.
Methods: This was a point prevalence study using a convenience sample of 500 patients with chronic obstructive pulmonary disease (COPD) from a single tertiary care outpatient respiratory clinic.
Results: Patients’ GOLD classification was determined based on symptoms (modified Medical Research Council [mMRC] dyspnea scale, COPD Assessment Test [CAT]), spirometry and self-reported exacerbation history. A total of 8.2% of patients were in the GOLD group A, 28.3% in group B, 4.2% in group C and 59.2% in group D.
Conclusions: In this 500 patient point prevalence study we report a low proportion of patients in GOLD group C and a high level of inhaled corticosteroids (ICS)/ long-acting beta2-agonist (LABA) and triple therapy use throughout all GOLD categories.
Clinical Implications: The GOLD guidelines have attempted to provide direction to practitioners by grouping patients into 4 groups based on symptoms and exacerbations however, the low prevalence of GOLD group C may indicate that not all of these groupings are clinically relevant. Future research is needed to better identify clinically relevant phenotypes that predict benefit from ICS and methods to promote guideline concordant management in COPD.
Citation
Citation: Safka KA, Wald J, Wang H, McIvor L, McIvor A. GOLD stage and treatment in COPD: A 500 patient point prevalence study. Chronic Obstr Pulm Dis (Miami). 2017; 4(1): 45-55. doi: http://doi.org/10.15326/jcopdf.4.1.2016.0126
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Jordan T. Perkins, MPH1 Radmila Choate, MPH1 David M. Mannino, MD1,2 Steven R. Browning, PhD, MSPH2 Robert A. Sandhaus, MD, PhD3
Author Affiliations
- Department of Preventive Medicine and Environmental Health, University of Kentucky College of Public Health, Lexington
- Department of Epidemiology, University of Kentucky College of Public Health, Lexington
- Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colorado
Address correspondence to:
David M. Mannino, MD
Department of Preventive Medicine and Environmental Health
University of Kentucky College of Public Health
111 Washington Avenue
Lexington, KY 40536
Phone: 859 218 2099
E-mail: dmannino@uky.edu
Abstract
Rationale: Alpha-1 antitrypsin deficiency (AATD) is characterized by decreased circulating levels or activity of the serum protein, alpha-1 antitrypsin, which increases risk for chronic lung or liver injury and may lead to diseases such as chronic obstructive pulmonary disease (COPD). Currently there is no cure for AATD, and it is largely controlled through disease management and augmentation therapy. This study was designed to describe characteristics of patients enrolled in a disease management and prevention program.
Methods: Data from questionnaires administered by AlphaNet were obtained on 4747 AATD patients and included demographic information, medical history, lifestyle choices, and adherence to the Alpha-1 Disease Management and Prevention Program (ADMAPP). A total of 1221 participants (25.72%) had missing adherence information and were excluded, leaving a final study population of 3526. Questionnaire answer dates ranged from May 29, 2008 to February 14, 2015. Logistic regression was used to adjust for demographic factors and comorbidities, comparing the populations stratified by adherence to ADMAPP.
Results: After adjustment for age, sex, race, Charlson Comorbidity Index, and income level, individuals who self-reported any adherence to ADMAPP were more likely to feel informed about their condition (odds ratio[OR]adj 4.95, 95% confidence interval[CI][3.24, 7.57]), and be taking preventive measures, such as smoking cessation (ORadj 0.47, 95% CI [0.31, 0.70]), appropriate immunizations, and self-reported exercise (ORadj 2.07, 95% CI [1.74, 2.47]).
Conclusions: This study suggests that ADMAPP may be a useful tool for informing and improving preventive measures taken by individuals with AATD. Future studies are needed to clarify the observed associations and study additional outcomes.
Citation
Citation: Perkins JT, Choate R, Mannino DM, Browning SR, Sandhaus RA. Benefits among patients with alpha-1 antitrypsin deficiency enrolled in a disease management and prevention program. Chronic Obstr Pulm Dis (Miami). 2017; 4(1): 56-64. doi: http://doi.org/10.15326/jcopdf.4.1.2016.0161
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