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Article: Strategies for Glycoengineering Therapeutic Proteins.

Dammen-Brower, Kris / Epler, Paige / Zhu, Stanley / Bernstein, Zachary J / Stabach, Paul R / Braddock, Demetrios T / Spangler, Jamie B / Yarema, Kevin J

Frontiers in chemistry

2022 Volume 10, Page(s) 863118

Abstract: ... by erythropoietin (EPO), enzymes (ectonucleotide pyrophosphatase 1, ENPP1), and IgG antibodies (e.g., afucosylated ...

Abstract	Almost all therapeutic proteins are glycosylated, with the carbohydrate component playing a long-established, substantial role in the safety and pharmacokinetic properties of this dominant category of drugs. In the past few years and moving forward, glycosylation is increasingly being implicated in the pharmacodynamics and therapeutic efficacy of therapeutic proteins. This article provides illustrative examples of drugs that have already been improved through glycoengineering including cytokines exemplified by erythropoietin (EPO), enzymes (ectonucleotide pyrophosphatase 1, ENPP1), and IgG antibodies (e.g., afucosylated Gazyva
Language	English
Publishing date	2022-04-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2711776-5
ISSN	2296-2646
ISSN	2296-2646
DOI	10.3389/fchem.2022.863118
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Article ; Online: Health System Approach to Improve Chronic Obstructive Pulmonary Disease Care after Hospital Discharge: Stepped-Wedge Clinical Trial.

Au, David H / Collins, Margaret P / Berger, Douglas B / Carvalho, Paula G / Nelson, Karin M / Reinke, Lynn F / Goodman, Richard B / Adamson, Rosemary / Woo, Deborah M / Rise, Peter J / Coggeshall, Scott S / Plumley, Robert B / Epler, Eric M / Moss, Brianna R / McDowell, Jennifer A / Weppner, William G

American journal of respiratory and critical care medicine

2022 Volume 205, Issue 11, Page(s) 1281–1289

Abstract: Rationale: ...

Abstract	Rationale:
MeSH term(s)	Hospitals ; Humans ; Patient Discharge ; Patient Readmission ; Pulmonary Disease, Chronic Obstructive ; Quality of Life
Language	English
Publishing date	2022-04-05
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202107-1707OC
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Article: Bronchiolitis obliterans organizing pneumonia.

Epler, G R

Archives of internal medicine

2001 Volume 161, Issue 2, Page(s) 158–164

Abstract: Bronchiolar disorders can be divided into 2 general categories: (1) airway disorders (cellular bronchiolitis and obliterative bronchiolitis) and (2) parenchymal disorders (respiratory bronchiolitis-interstitial lung disease, which occurs in smokers and ... ...

Abstract	Bronchiolar disorders can be divided into 2 general categories: (1) airway disorders (cellular bronchiolitis and obliterative bronchiolitis) and (2) parenchymal disorders (respiratory bronchiolitis-interstitial lung disease, which occurs in smokers and is treatable with smoking cessation or corticosteroid therapy, and bronchiolitis obliterans organizing pneumonia, an inflammatory lung disease simultaneously involving the terminal bronchioles and alveoli). This article reviews the clinical findings and therapeutic management of bronchiolitis obliterans organizing pneumonia.
MeSH term(s)	Cryptogenic Organizing Pneumonia/classification ; Cryptogenic Organizing Pneumonia/diagnosis ; Cryptogenic Organizing Pneumonia/pathology ; Cryptogenic Organizing Pneumonia/therapy ; Humans
Language	English
Publishing date	2001-01-22
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	211575-x
ISSN	1538-3679 ; 0003-9926 ; 0888-2479 ; 0730-188X
ISSN (online)	1538-3679
ISSN	0003-9926 ; 0888-2479 ; 0730-188X
DOI	10.1001/archinte.161.2.158
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Article: Primary Care Provider Experience With Proactive E-Consults to Improve COPD Outcomes and Access to Specialty Care.

Spece, Laura J / Weppner, William G / Weiner, Bryan J / Collins, Margaret / Adamson, Rosemary / Berger, Douglas B / Nelson, Karin M / McDowell, Jennifer / Epler, Eric / Carvalho, Paula G / Woo, Deborah M / Donovan, Lucas M / Feemster, Laura C / Au, David H / Sayre, George

Chronic obstructive pulmonary diseases (Miami, Fla.)

2022 Volume 10, Issue 1, Page(s) 46–54

Abstract: Background: Often patients with chronic obstructive pulmonary disease (COPD) receive poor quality care with limited access to pulmonologists. We tested a novel intervention, INtegrating Care After Exacerbation of COPD (InCasE), that improved patient ... ...

Abstract	Background: Often patients with chronic obstructive pulmonary disease (COPD) receive poor quality care with limited access to pulmonologists. We tested a novel intervention, INtegrating Care After Exacerbation of COPD (InCasE), that improved patient outcomes after hospitalization for COPD. InCasE used population-based identification of patients for proactive e-consultation by pulmonologists, and tailored recommendations with pre-populated orders timed to follow-up with primary care providers (PCPs). Although adoption by PCPs was high, we do not know how PCPs experienced the intervention. Objective: Our objective was to assess PCPs' experience with proactive pulmonary e-consults after hospitalization for COPD. Methods: We conducted a convergent mixed methods study among study PCPs at 2 medical centers and 10 outpatient clinics. PCPs underwent semi-structured interviews and surveys. We performed descriptive analyses on quantitative data and inductive and deductive coding based on prespecified themes of acceptability, appropriateness, and feasibility for qualitative data. Key results: We conducted 10 interviews and 37 PCPs completed surveys. PCPs perceived InCasE to be acceptable and feasible. Facilitators included the proactive consult approach to patient identification and order entry. PCPs also noted the intervention was respectful and collegial. PCPs had concerns regarding appropriateness related to an unclear role in communicating recommendations to patients. PCPs also noted a potential decrease in autonomy if overused. Conclusion: This evaluation indicates that a proactive e-consult intervention can be deployed to collaboratively manage the health of populations with COPD in a way that is acceptable, appropriate, and feasible for primary care. Lessons learned from this study suggest the intervention may be transferable to other settings and specialties.
Language	English
Publishing date	2022-12-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2771715-X
ISSN	2372-952X
ISSN	2372-952X
DOI	10.15326/jcopdf.2022.0357
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Article: Heterogeneity of bronchiolitis obliterans organizing pneumonia.

Epler, G R

Current opinion in pulmonary medicine

1998 Volume 4, Issue 2, Page(s) 93–97

Abstract: Reports of the characterization and understanding of bronchiolitis obliterans organizing pneumonia (BOOP) have continued at an accelerated rate for several years. The radiographic and high-resolution CT features of BOOP continue to be documented. There ... ...

Abstract	Reports of the characterization and understanding of bronchiolitis obliterans organizing pneumonia (BOOP) have continued at an accelerated rate for several years. The radiographic and high-resolution CT features of BOOP continue to be documented. There have been new insights into the pathogenesis of BOOP. An animal model has been developed. Video-assisted thoracoscopic biopsy has become a standard for confirming the diagnosis. Childhood BOOP has been described in several reports. Idiopathic BOOP continues to be the most common type; however, a variety of clinical settings such as inhalation of mold spores and associated disorders such as renal transplantation continue to be described. This paper provides an update of advances in the pathogenesis, radiographic features, clinical course, and categorization of the heterogeneity of BOOP.
MeSH term(s)	Adolescent ; Adult ; Animals ; Anti-Bacterial Agents/therapeutic use ; Bone Marrow Transplantation/adverse effects ; Child ; Child, Preschool ; Coloring Agents/adverse effects ; Cryptogenic Organizing Pneumonia/diagnosis ; Cryptogenic Organizing Pneumonia/drug therapy ; Cryptogenic Organizing Pneumonia/etiology ; Female ; Humans ; Kidney Transplantation/adverse effects ; Lung Transplantation/adverse effects ; Male ; Prednisone/therapeutic use ; Prognosis ; Tomography, X-Ray Computed
Chemical Substances	Anti-Bacterial Agents ; Coloring Agents ; Prednisone (VB0R961HZT)
Language	English
Publishing date	1998-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1285505-4
ISSN	1531-6971 ; 1070-5287 ; 1078-1641
ISSN (online)	1531-6971
ISSN	1070-5287 ; 1078-1641
DOI	10.1097/00063198-199803000-00006
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Article: Bronchiolar disorders with airflow obstruction.

Epler, G R

Current opinion in pulmonary medicine

1996 Volume 2, Issue 2, Page(s) 134–140

Abstract: Bronchiolar lesions continue to be increasingly recognized as a cause of airflow obstruction. Thus, it is important to have a current update of the current clinical, radiographic, and immunologic perspective of these disorders. Diffuse panbronchiolitis ... ...

Abstract	Bronchiolar lesions continue to be increasingly recognized as a cause of airflow obstruction. Thus, it is important to have a current update of the current clinical, radiographic, and immunologic perspective of these disorders. Diffuse panbronchiolitis has been reported to occur in the United States and Europe, and the anti-inflammatory action of erythromycin appears to be effective in management. Idiopathic bronchiolitis obliterans, post-fume or post-infectious, or connective tissue disorder bronchiolitis obliterans continues to be rare and often has a poor prognosis. Lung transplantation bronchiolitis obliterans continues to be the major complication and cause of mortality in transplant recipients. Risk factors of this form of chronic rejection include more frequent and more severe acute rejection and the coexistence of organizing pneumonia. The recognition of the distinctive differences among the bronchiolar airflow disorders continues to be essential for improved patient care, greater understanding of the pathogenesis, and development of therapeutic advances.
MeSH term(s)	Acute Disease ; Airway Obstruction/diagnostic imaging ; Airway Obstruction/etiology ; Airway Obstruction/immunology ; Airway Obstruction/physiopathology ; Anti-Bacterial Agents/therapeutic use ; Anti-Inflammatory Agents/therapeutic use ; Bacterial Infections ; Bronchial Diseases/complications ; Bronchial Diseases/diagnostic imaging ; Bronchial Diseases/immunology ; Bronchial Diseases/physiopathology ; Bronchiolitis/complications ; Bronchiolitis/diagnostic imaging ; Bronchiolitis/drug therapy ; Bronchiolitis/immunology ; Bronchiolitis/physiopathology ; Bronchiolitis Obliterans/etiology ; Bronchiolitis Obliterans/mortality ; Bronchiolitis Obliterans/physiopathology ; Cause of Death ; Chronic Disease ; Connective Tissue Diseases/complications ; Connective Tissue Diseases/physiopathology ; Erythromycin/therapeutic use ; Graft Rejection/complications ; Humans ; Lung Transplantation/adverse effects ; Lung Transplantation/mortality ; Pneumonia/complications ; Prognosis ; Radiography ; Risk Factors ; Smoking/adverse effects
Chemical Substances	Anti-Bacterial Agents ; Anti-Inflammatory Agents ; Erythromycin (63937KV33D)
Language	English
Publishing date	1996-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1285505-4
ISSN	1531-6971 ; 1070-5287 ; 1078-1641
ISSN (online)	1531-6971
ISSN	1070-5287 ; 1078-1641
DOI	10.1097/00063198-199603000-00010
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Article: Bronchiolitis obliterans organizing pneumonia.

Epler, G R

Seminars in respiratory infections

1995 Volume 10, Issue 2, Page(s) 65–77

Abstract: Bronchiolitis obliterans organizing pneumonia (BOOP) is increasingly recognized as an important cause of diffuse infiltrative lung disease. It is a diagnostic consideration in patients with a febrile flu-like illness of a few weeks' duration and a ... ...

Abstract	Bronchiolitis obliterans organizing pneumonia (BOOP) is increasingly recognized as an important cause of diffuse infiltrative lung disease. It is a diagnostic consideration in patients with a febrile flu-like illness of a few weeks' duration and a roentgenogram showing bilateral patchy infiltrates that are not responsive to a typical course of antibiotics. It is defined as granulated tissue plugs within lumens of small airways that extend into alveolar ducts and alveoli. Clinically, a flu-like illness, cough, and crackles are common. Pulmonary function studies of patients show a decreased vital capacity, normal flow rates (except in smokers), and a decreased diffusing capacity. It is generally idiopathic, but it may occur during the resolution of a viral or mycoplasma pneumonia. It is also associated with a variety of systemic illnesses and clinical settings. These include the connective tissue disorders, antineoplastic and other drugs, and immunological disorders, as well as bone marrow and lung transplantation. There are numerous related disorders, including human immunodeficiency virus infection, radiation therapy, thyroiditis, and alcoholic cirrhosis. In idiopathic BOOP, complete resolution occurs in 65% to 85% of patients treated with corticosteroid therapy. This type of therapy is often effective in patients with associated systemic disorders or in other clinical settings, but there may be limited or no response in patients with dermatomyositis, immunosuppression, or interstitial opacities at the lung bases. Respiratory failure leading to death may occur in 5% of patients. It is important to add BOOP to the differential diagnosis of febrile, noninfectious illnesses that are mimics of pneumonia.
MeSH term(s)	Adult ; Arthritis, Rheumatoid/complications ; Bone Marrow Transplantation/adverse effects ; Connective Tissue Diseases/complications ; Cryptogenic Organizing Pneumonia/classification ; Cryptogenic Organizing Pneumonia/diagnosis ; Cryptogenic Organizing Pneumonia/etiology ; Diagnosis, Differential ; Female ; Humans ; Immune System Diseases/complications ; Lung/pathology ; Lung Transplantation/adverse effects ; Male ; Middle Aged ; Pneumonia/diagnosis ; Pneumonia, Mycoplasma/complications ; Pneumonia, Viral/complications ; Radiography, Thoracic ; Tomography, X-Ray Computed
Language	English
Publishing date	1995-06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	632947-0
ISSN	0882-0546
ISSN	0882-0546
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Article: Bronchiolitis with airflow obstruction.

Epler, G R

Current opinion in pulmonary medicine

1995 Volume 1, Issue 2, Page(s) 109–118

Abstract: Bronchiolar lesions are becoming increasingly recognized as an important cause of airflow obstruction. For this reason, it is helpful to have an update of the current clinical, radiographic, and immunologic perspective. Among the bronchiolar airflow ... ...

Abstract	Bronchiolar lesions are becoming increasingly recognized as an important cause of airflow obstruction. For this reason, it is helpful to have an update of the current clinical, radiographic, and immunologic perspective. Among the bronchiolar airflow disorders, diffuse panbronchiolitis is related to HLA antigen Bw54, and low-dose, long-term erythromycin appears to be effective therapy. Bronchiolitis obliterans can be classified histologically as constrictive bronchiolitis and as proliferative bronchiolitis obliterans. Idiopathic, postfume, postinfectious, and connective tissue disease bronchiolitis obliterans continue to be rare and often have a poor prognosis. Bronchiolitis obliterans associated with lung transplantation is undergoing intensive investigation with regard to pathogenesis, immunologic study, early detection, and treatment. The lesion appears to be a form of chronic organ rejection. The recognition of the distinctive differences among the bronchiolar airflow disorders by clinicians and clinical investigators is essential for improved patient care, for a greater understanding of the pathogenesis of the disorder, and for development of new therapeutic advances.
MeSH term(s)	Airway Obstruction/physiopathology ; Animals ; Bone Marrow Transplantation/adverse effects ; Bronchiolitis/classification ; Bronchiolitis/etiology ; Bronchiolitis/pathology ; Bronchiolitis/physiopathology ; Bronchiolitis Obliterans/classification ; Bronchiolitis Obliterans/diagnosis ; Bronchiolitis Obliterans/pathology ; Heart-Lung Transplantation ; Humans ; Lung Transplantation/adverse effects ; Prognosis
Language	English
Publishing date	1995-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1285505-4
ISSN	1531-6971 ; 1070-5287 ; 1078-1641
ISSN (online)	1531-6971
ISSN	1070-5287 ; 1078-1641
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Article ; Online: Temporal correspondence of selenium and mercury, among brine shrimp and water in Great Salt Lake, Utah, USA.

Wright, Jacob / Yang, Shu / Johnson, William P / Black, Frank J / McVey, James / Epler, Austin / Scott, Abigail F / Trentman, Madelene P / Martin, Alexandria R / Pandey, Gaurav / Piskadlo, Andrew M

The Science of the total environment

2020 Volume 749, Page(s) 141273

Abstract: The specific source of high burdens of selenium (Se) and mercury (Hg) in several bird species at Great Salt Lake (GSL) remain unknown. Frequent co-located water and brine shrimp samples were collected during 2016 through 2017 to identify potential ... ...

Abstract	The specific source of high burdens of selenium (Se) and mercury (Hg) in several bird species at Great Salt Lake (GSL) remain unknown. Frequent co-located water and brine shrimp samples were collected during 2016 through 2017 to identify potential correlations of element concentrations among brines and brine shrimp, a keystone species in the GSL. Like many aquatic systems, GSL is characterized by elevated methylmercury (MeHg) in deep waters. However, in contrast to thermally-stratified aquatic systems, biota in the salinity-stratified GSL do not reside in its deep waters, obscuring the presumed relationship between elevated MeHg in biota and in the deep brine. Brine shrimp and water column (shallow and deep, filtered and unfiltered) samples were collected from six sites spanning the South Arm of GSL approximately every other month. Mercury concentrations in brine shrimp (on average 89% of which is MeHg) were correlated only with total mercury in surface filtered water, and displayed little spatial variability, but consistent seasonal trends across the two sampled years. In contrast to Hg, temporal correspondence was observed between Se concentrations in brine shrimp and those in all water samples regardless of filtering and depth, with maxima and minima at higher-than-seasonal frequency. The data suggest a spatially diffuse source of bioavailable mercury to the shallow brine that responds to seasonal influences, for which the underlying deep brine, surficial sediments, and overlying atmosphere were evaluated in terms of potential temporal correspondence to shallow brine and brine shrimp Hg concentrations, as well as potential to mix across the extent of the shallow brine. Bioaccumulation factors were at the low end of those reported for marine systems, and decreased at higher trace element concentrations in water.
MeSH term(s)	Animals ; Artemia ; Environmental Monitoring ; Lakes ; Mercury/analysis ; Methylmercury Compounds ; Selenium/analysis ; Utah ; Water ; Water Pollutants, Chemical/analysis
Chemical Substances	Methylmercury Compounds ; Water Pollutants, Chemical ; Water (059QF0KO0R) ; Mercury (FXS1BY2PGL) ; Selenium (H6241UJ22B)
Language	English
Publishing date	2020-07-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	121506-1
ISSN	1879-1026 ; 0048-9697
ISSN (online)	1879-1026
ISSN	0048-9697
DOI	10.1016/j.scitotenv.2020.141273
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Article ; Online: Strategies for Glycoengineering Therapeutic Proteins

Kris Dammen-Brower / Paige Epler / Stanley Zhu / Zachary J. Bernstein / Paul R. Stabach / Demetrios T. Braddock / Jamie B. Spangler / Kevin J. Yarema

Frontiers in Chemistry, Vol

2022 Volume 10

Abstract: ... by erythropoietin (EPO), enzymes (ectonucleotide pyrophosphatase 1, ENPP1), and IgG antibodies (e.g., afucosylated ...

Abstract	Almost all therapeutic proteins are glycosylated, with the carbohydrate component playing a long-established, substantial role in the safety and pharmacokinetic properties of this dominant category of drugs. In the past few years and moving forward, glycosylation is increasingly being implicated in the pharmacodynamics and therapeutic efficacy of therapeutic proteins. This article provides illustrative examples of drugs that have already been improved through glycoengineering including cytokines exemplified by erythropoietin (EPO), enzymes (ectonucleotide pyrophosphatase 1, ENPP1), and IgG antibodies (e.g., afucosylated Gazyva®, Poteligeo®, Fasenra™, and Uplizna®). In the future, the deliberate modification of therapeutic protein glycosylation will become more prevalent as glycoengineering strategies, including sophisticated computer-aided tools for “building in” glycans sites, acceptance of a broad range of production systems with various glycosylation capabilities, and supplementation methods for introducing non-natural metabolites into glycosylation pathways further develop and become more accessible.
Keywords	glycoengineering ; pharmacodynamics ; pharmacokinetics ; therapeutic ; glycosylation ; N-glycans ; Chemistry ; QD1-999
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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