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Margaret A. Hay, MD1 Kristen E. Holm, PhD2,3 Jean McCathern,2 Robert A. Sandhaus, MD, PhD2,3 Charlie Strange, MD1,2
Author Affiliations
- Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, South Carolina, United States
- AlphaNet, Inc., Coral Gables, Florida, United States
- Department of Medicine, National Jewish Health, Denver, Colorado, United States
Address correspondence to:
Charlie Strange, MD
MSC630
Medical University of South Carolina
Charleston, SC, 29425
Phone: (843) 792-3174
Email: strangec@musc.edu
Abstract
Background: Individuals with alpha-1 antitrypsin deficiency (AATD)-associated chronic obstructive pulmonary disease (COPD) may be at increased risk of coronavirus disease 2019 (COVID-19) pneumonia since COPD is associated with an increased risk of severe COVID-19 infection.
Research Question: We hypothesized that the AlphaNet disease management program would lower COVID-19 burdens. We evaluated the prevalence of COVID-19 infection, severe COVID-19, interruptions in augmentation therapy, and intention to vaccinate.
Study Design and Methods: Data regarding COVID-19 were collected monthly from March 2020 through February 2022. Responses from 8019 individuals were analyzed to evaluate the prevalence and severity of COVID-19 infections, interruptions in AATD care, and the likelihood of vaccination.
Results: By the end of 2020, 4% of patients reported a positive COVID-19 test. Of those, 35.3% were hospitalized, with 8.6% admitted to the intensive care unit (ICU). By February 2022, the prevalence of COVID-19 infections had increased to 18.6%, with hospitalization rates of 22.1% and ICU admissions at 4.7%. Attitudes about COVID-19 vaccination assessed in December 2020 before the vaccine was widely available suggested 10.3% of patients would definitely not get the vaccine. Notably, 38.2% of those subsequently self-reported receipt of a COVID-19 vaccine.
Interpretation: The prevalence of COVID-19 infections in patients with AATD was lower than the prevalence in the general U.S. population during 2020, although with a higher hospitalization rate. This health-managed population has a high vaccination intent. Those with an initially low vaccination intent changed their minds over time. We interpret these results as showing that most AlphaNet individuals with AATD had success at navigating the COVID-19 pandemic with lower case rates than the general U.S. population.
Citation
Citation: Hay M, Holm KE, McCathern J, Sandhaus RA, Strange C. Impact of coronavirus disease 2019 and vaccination attitudes on alpha-1 antitrypsin deficiency. Chronic Obstr Pulm Dis. 2023; 10(4): 335-342. doi: http://dx.doi.org/10.15326/jcopdf.2023.0406
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Sandra E. Zaeh, MD, MS1 Meredith Case, MD, MBE2 David H. Au, MD, MS3,4 Michele DaSilva, MSEd, RRT, RRT-NPS5 Karen Deitemeyer 5 Julie DeLisa, MA6 Laura C. Feemster, MD, MS3,4 Lynn B. Gerald, PhD6,7 Jerry A. Krishnan, MD, PhD6,7 Jennifer Sculley, MDes7 Annette Woodruff, BS5 Michelle N. Eakin, PhD2
Author Affiliations
- Division of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine, New Haven, Connecticut, United States
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, United States
- Veterans Affairs Puget Sound Health Services Research and Development, Center of Innovation for Veteran-Centered and Value-Driven Care, Seattle, Washington, United States
- Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, Washington, United States
- Patient Advisory Board, American Lung Association, Chicago, Illinois, United States
- Division of Pulmonary, Critical Care, Sleep, and Allergy, Department of Medicine, University of Illinois Chicago, Chicago, Illinois, United States
- Office of Population Health Sciences, University of Illinois-Chicago, Chicago, Illinois, United States
Address correspondence to:
Sandra E. Zaeh, MD, MS
Division of Pulmonary, Critical Care, and Sleep Medicine
Yale University School of Medicine
333 Cedar Street
New Haven, CT 06510
Phone: (908) 938-0982
E-mail: sandra.zaeh@yale.edu
Abstract
Purpose: While home oxygen therapy increases survival in patients with chronic obstructive pulmonary disease (COPD) who have severe resting hypoxemia, recent evidence suggests that there is no survival benefit of home oxygen for patients with COPD who have isolated exertional desaturation. We aimed to understand clinician practice patterns surrounding the prescription of home oxygen for patients with COPD.
Methods: We conducted semi-structured qualitative interviews via videoconference with 15 physicians and 3 nurse practitioners who provide care for patients with COPD. Clinicians were recruited through the American Lung Association Airways Clinical Research Centers. Interview guides were created with the assistance of patient investigators and included questions regarding clinician practices surrounding the prescription of oxygen for patients with COPD and the use of clinical guidelines. Interviews were recorded, transcribed, and coded for themes.
Results: Of the 18 clinician interviewees, one-third were women, with most participants (n=11) being < 50 years old. Results of the semi-structured interviews suggested research evidence, clinical experience, and patient preferences contributed to clinician decision-making. Most clinicians described a shared decision-making process for prescribing home oxygen for patients, including discussion of risks and benefits, and developing an understanding of patient values and preferences. Clinicians did not use a structured tool to conduct these conversations.
Conclusion: Clinicians consider a number of patient and clinical factors when prescribing home oxygen therapy, often using a shared decision-making process. Tools to support shared decision-making about the use of home oxygen are needed.
Citation
Citation: Zaeh SE, Case M, Au DH, et al. Clinical practices surrounding the prescription of home oxygen in patients with COPD and desaturation. Chronic Obstr Pulm Dis. 2023; 10(4): 343-354. doi: http://dx.doi.org/10.15326/jcopdf.2023.0402
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Junxiang Chen, PhD1 Zhonghui Xu, MS2 Li Sun, MS1 Ke Yu, MS1 Craig P. Hersh, MD, MPH2,3 Adel Boueiz, MD, MS2,3 John E. Hokanson, MPH, PhD4 Frank C. Sciurba, MD5 Edwin K. Silverman MD, PhD,2,3 Peter J. Castaldi, MD, MS2,6* Kayhan Batmanghelich, PhD1*
Author Affiliations
- Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, United States
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, United States
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
- Division of General Internal Medicine and Primary Care, Brigham and Women’s Hospital, Boston, Massachusetts, United States
* Equal contribution
Address correspondence to:
Junxiang Chen, PhD
Department of Biomedical Informatics
University of Pittsburgh
5607 Baum Blvd
Pittsburgh, PA 15206
Phone: (412) 624-5100
Email: juc91@pitt.edu
Abstract
Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by pathologic changes in the airways, lung parenchyma, and persistent inflammation, but the links between lung structural changes and blood transcriptome patterns have not been fully described.
Objectives: The objective of this study was to identify novel relationships between lung structural changes measured by chest computed tomography (CT) and blood transcriptome patterns measured by blood RNA sequencing (RNA-seq).
Methods: CT scan images and blood RNA-seq gene expression from 1223 participants in the COPD Genetic Epidemiology (COPDGene®) study were jointly analyzed using deep learning to identify shared aspects of inflammation and lung structural changes that we labeled image-expression axes (IEAs). We related IEAs to COPD-related measurements and prospective health outcomes through regression and Cox proportional hazards models and tested them for biological pathway enrichment.
Results: We identified 2 distinct IEAs: IEAemph which captures an emphysema-predominant process with a strong positive correlation to CT emphysema and a negative correlation to forced expiratory volume in 1 second and body mass index (BMI); and IEAairway which captures an airway-predominant process with a positive correlation to BMI and airway wall thickness and a negative correlation to emphysema. Pathway enrichment analysis identified 29 and 13 pathways significantly associated with IEAemph and IEAairway, respectively (adjusted p<0.001).
Conclusions: Integration of CT scans and blood RNA-seq data identified 2 IEAs that capture distinct inflammatory processes associated with emphysema and airway-predominant COPD.
Citation
Citation: Chen J, Xu Z, Sun L, et al. Deep learning integration of chest computed tomography and gene expression identifies novel aspects of COPD. Chronic Obstr Pulm Dis. 2023; 10(4): 355-368. doi: http://dx.doi.org/10.15326/jcopdf.2023.0399
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Jamuna K. Krishnan, MD, MBA, MS1 Sonal G. Mallya, MD2,3 Musarrat Nahid, MSc3 Aaron D. Baugh, MD4 MeiLan K. Han, MD, MS5 Kerri I. Aronson, MD, MS1 Parag Goyal MD, MS3,6 Laura C. Pinheiro, MPH, PhD3 Samprit Banerjee, PhD7 Fernando J. Martinez, MD, MS1 Monika M. Safford, MD3
Author Affiliations
- Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, New York, United States
- Division of Pulmonary and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
- Division of General Internal Medicine, Weill Cornell Medicine, New York, New York, United States
- Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, University of California San Francisco, San Francisco, California, United States
- Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor, Michigan, United States
- Division of Cardiology, Weill Cornell Medicine, New York, New York, United States
- Department of Population Health Sciences, Weill Cornell Medicine, New York, New York, United States
Address correspondence to:
Jamuna K. Krishnan, MD
Division of Pulmonary and Critical Care Medicine
Weill Cornell Medicine
1305 York Avenue Y-1047, Box 96
Phone: (646) 962-2333
Email: jkk9002@med.cornell.edu
Abstract
Rationale: Cardiovascular disease (CVD) affects the prognosis of patients with chronic obstructive pulmonary disease (COPD). Black women with COPD have a disproportionate risk of CVD-related mortality, yet disparities in CVD prevention in COPD are unknown.
Objectives: We aimed to identify race-sex differences in the receipt of statin treatment for CVD prevention, and whether these differences were explained by factors influencing health care utilization in the REasons for Geographic And Racial Differences in Stroke (REGARDS) COPD study sub-cohort.
Methods: We conducted a cross-sectional analysis among REGARDS Medicare beneficiaries with COPD. Our primary outcome was the presence of statin on in-home pill bottle review among individuals with an indication. Prevalence ratios (PR) for statin treatment among race-sex groups compared to White men were estimated using Poisson regression with robust variance. We then adjusted for covariates previously shown to impact health care utilization.
Results: Of the 2032 members within the COPD sub-cohort with sufficient data, 1435 participants (19% Black women, 14% Black men, 28% White women, and 39% White men) had a statin indication. All race-sex groups were less likely to receive statins than White men in unadjusted models. After adjusting for covariates that influence health care utilization, Black women (PR 0.76, 95% confidence interval [CI] 0.67 to 0.86) and White women (PR 0.84 95% CI 0.76 to 0.91) remained less likely to be treated compared to White men.
Conclusion: All race-sex groups were less likely to receive statin treatment in the REGARDS COPD sub-cohort compared to White men. This difference persisted in women after controlling for individual health care utilization factors, suggesting structural interventions are needed.
Citation
Citation: Krishnan JK, Mallya SG, Nahid M, et al. Disparities in guideline-concordant statin treatment in individuals with COPD. Chronic Obstr Pulm Dis. 2023; 10(4): 369-379. doi: http://dx.doi.org/10.15326/jcopdf.2023.0395
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Andrew J. Devine, BS*1 Noah J. Smith, BS*2 Rashika Joshi, MD1 Qiang Fan, PhD1 Michael T. Borchers, PhD1,3 Geremy C. Clair, PhD4 Joshua N. Adkins, PhD4 Brian M. Varisco, MD1,2,5,6
Author Affiliations
- Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
- University of Cincinnati School of Medicine, Cincinnati, Ohio, United States
- Division of Pulmonary and Critical Care Medicine, University of Cincinnati, Cincinnati, Ohio, United States
- Pacific Northwest National Laboratory, Richland, Washington, United States
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
- Arkansas Children's Research Institute, Little Rock, Arkansas, United States
* Authors contributed equally
Address correspondence to:
Brian Varisco, MD
Arkansas Children's Research Institute
13 Children's Way
Little Rock, AR 72202
Phone: (501) 364-7373
Email: BVarisco@uams.edu
Abstract
Chymotrypsin-like elastase 1 (CELA1) is a serine protease that is neutralized by alpha-1antitrypsin (AAT) and prevents emphysema in a murine antisense oligonucleotide model of AAT-deficient emphysema. Mice with genetic ablation of AAT do not have emphysema at baseline but develop emphysema with injury and aging. We tested the role of the CELA1 gene in emphysema development in this genetic model of AAT-deficiency following tracheal lipopolysaccharide (LPS), 10 months of cigarette smoke exposure, aging, and a low-dose tracheal porcine pancreatic elastase (LD-PPE) model we developed. In this last model, we performed proteomic analysis to understand differences in lung protein composition. We were unable to show that AAT-deficient mice developed more emphysema than wild type with escalating doses of LPS. In the LD-PPE model, AAT-deficient mice developed significant and progressive emphysema from which Cela1-/- & AAT-deficient mice were protected. Cela1-/-& AAT-deficient lungs had more matrix-associated proteins than AAT-deficientlungs but also had more leukocyte-associated proteases. With cigarette smoke exposure, Cela1-/- &AAT-deficient mice had more emphysema than AAT-deficient mice but had less myeloperoxidase activity. Cela1-/-&AAT-deficient mice had less age-related airspace simplification than AAT-deficient and were comparable to wild type. While CELA1 promotes inflammation-independent emphysema progression and its absence preserves the lung matrix in multiple models of AAT-deficient emphysema, for unclear reasons Cela1 deficiency is associated with increased emphysema with cigarette smoke. While anti-CELA1 therapies could potentially be used to prevent emphysema progression in AAT deficiency after smoking cessation, an understanding of why and how cigarette smoke exacerbates emphysema in Cela1 deficiency and whether AAT replacement therapy mitigates this effect is needed first.
Citation
Citation: Devine AJ, Smith NJ, Joshi R, et al. Chymotrypsin-like elastase-1 mediates progressive emphysema in alpha-1 antitrypsin deficiency. Chronic Obstr Pulm Dis. 2023; 10(4): 380-391. doi: http://dx.doi.org/10.15326/jcopdf.2023.0416
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Charlie Strange, MD1,2 Sheri Allison2 Jean McCathern2 Robert A. Sandhaus, MD, PhD2,3 Kristen E. Holm, PhD, MPH2,3
Author Affiliations
- Medical University of South Carolina, Charleston, South Carolina, United States
- AlphaNet, Inc., Coral Gables, Florida, United States
- National Jewish Health, Denver, Colorado, United States
Address correspondence to:
Charlie Strange, MD
MSC630
Medical University of South Carolina
Charleston, SC 29425
Email: strangec@musc.edu
Abstract
Background: Currently approved therapies for individuals with alpha-1 antitrypsin deficiency (AATD) are intravenously infused products. The burdens and demographics of infusion practices in the United States are not well-characterized.
Research Question: What is the prevalence of different infusion practices in the United States?
Study Design and Methods: AlphaNet disease management participants completed a survey that captured current and past infusion practices. Data regarding the reasons for choosing their current infusion practice, problems with past infusion practices, resources required, and support services utilized were collected from February 8, 2022 through July 1, 2022.
Results: Among 5266 individuals, infusions happened at home by health care providers (60.2%), at infusion clinics (30.6%), and by self-infusion (8.1%). Self-infusion prevalence increased with time on therapy and was more prevalent in younger individuals (61.2 ± 10.5 years) compared to users of other infusion practices (64.1 ± 11.0 years), (p<0.001). The perceived benefits of self-infusion included: (1) freedom and flexibility (77.9%), (2) ability to travel (44.5%), (3) avoidance of infusion clinics (41.8%), (4) time-savings (35.9%), (5) less absence from work (26.6%), (6) less exposure to infections (22.1%), and (7) less cost (16.4%). Self-infusion was done through permanent intravenous catheters in 41.2% and peripheral intravenous catheters in 58.3%. Self-infusers were more satisfied (93.1% “very satisfied”) than other groups. Among individuals currently infusing with home nurses or in clinics, 21.4% would consider self-infusing in the future.
Interpretation: Self-infusion of alpha-1 antitrypsin is feasible and associated with high satisfaction scores. Recommendations for catheter care, infusion support, and cost management are informed by survey results.
Citation
Citation: Strange C, Allison S, McCathern J, Sandhaus RA, Holm KE. Augmentation therapy for alpha-1 antitrypsin deficiency: patient experiences with self-infusion, home providers, and clinics. Chronic Obstr Pulm Dis. 2023; 10(4): 392-399. doi: http://dx.doi.org/10.15326/jcopdf.2023.0430
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Meimei Xu, PhD1 Jiajia Wang, PhD2 Lianhui Shan, MS1 Xinying An, PhD1
Author Affiliations
- Institute of Medical Information, Chinese Academy of Medical Sciences, Beijing, China
- Department of Occupational and Environmental Health, School of Public Health, Capital Medical University, Beijing, China
Abstract
Background: Despite studies investigating the publication rates and factors influencing publication outcomes of clinical trials in some disease fields, there is a notable lack of research focusing on chronic obstructive pulmonary disease (COPD) clinical trials. This study aims to explore the characteristics of COPD-related clinical trials and identify factors associated with publication status and publication time.
Methods: A systematic search was conducted on the World Health Organization International Clinical Trials Registry Platform on April 28, 2022, to identify completed interventional clinical trials related to COPD. Various trial features were analyzed, and factors influencing publication status and time were examined.
Results: A total of 2577 completed interventional clinical trials focusing on COPD were identified. A total of 42.76% of trials enrolled ≤50 participants. The majority of trials were randomized (81.72%), blind (57.39%), parallel-assignment (59.14%), single-center (51.30%), multi-arm (83.86%), nonindustry funded (52.00%), and conducted for therapeutic purposes (73.11%). The 2-year cumulative publication rate was found to be 27.9%. The median time of study duration, dissemination lag, and publication lag were 17.27, 21.07, and 24.70 months, respectively. Multivariate analysis revealed that sample size, blind design, and study phase significantly influenced the likelihood of publication, while intervention model, primary purpose, study phase, funder, and study duration were significant factors affecting publication time.
Conclusion: The findings highlight the inadequacy of large multi-center interventional clinical trials for COPD and indicate a low 2-year cumulative publication rate. Strengthening collaboration among investigators and adopting scientifically robust designs for larger phase 3 clinical trials are crucial to advancing COPD research and enhancing publication outcomes.
Citation
Citation: Xu M, Wang J, Shan L, An X. The current landscape of COPD-related clinical trials registered on the World Health Organization's International Clinical Trials Registry Platform: a comprehensive analysis of study characteristics and publication status. Chronic Obstr Pulm Dis. 2023; 10(4): 400-411. doi: http://dx.doi.org/10.15326/jcopdf.2023.0417
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Narjes Soleimanifar, PhD1 Sara Assadiasl, MD, PhD1 Effat Kalateh, MD2 Mohammad Sadegh Hassanvand, PhD3 Maryam Sadr, MS1 Hanieh Mojtahedi, MS1 Kazem Nadafi, PhD3 Mohammad Hossein Nicknam, MD, PhD1 Maryam Edalatifard, MD2
Author Affiliations
- Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Thoracic Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
- Center for Air Pollution Research, Institute for Environmental Research, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran
Address correspondence to:
Maryam Edalatifard, MD
Thoracic Research Center
Imam Khomeini Hospital
Tehran University of Medical Sciences
Tehran, Iran
Email: m-edalatifard@tums.ac.ir
Abstract
Background: Chronic obstructive pulmonary disease (COPD) is characterized by progressive obstruction of airways due to chronic inflammation. Both genetic and environmental components are risk factors for COPD. The most common cause of COPD is smoking. However, evidence suggests that 17% to 38% of COPD patients are nonsmokers, so other factors like air pollution may also play a role.
Objective: The relationship between serum exosomes and exposure to particulate matter (PM) <2.5 and 10 micrometers (µm) in the residing environment of COPD patients and healthy groups was investigated. The correlation between inflammatory cytokine levels with exosome count was also studied.
Methods: Peripheral blood samples were taken from 20 COPD patients without a smoking history or a family history of COPD, along with 20 nonsmoker healthy controls. The serum exosomes were counted by flow cytometry using a CD81 marker. The exposure to PM2.5 and PM10 was measured in daily, weekly, and monthly intervals based on the longitudinal measurements of the monitoring stations, and the correlation between exosome count and air pollutants was analyzed.
Results: The serum CD81+ exosome count in COPD patients was significantly elevated compared to the healthy controls and this was correlated with daily PM10 (P-value=0.02) and monthly PM2.5 (P-value=0.02) exposure. Although interferon-gamma levels of COPD patients were higher than healthy controls, there was no correlation between exosome count and cytokine level.
Conclusion: Considering the significant relationship between air pollutants and the count of serum exosomes demonstrated in the present study, air pollution might be a considerable risk factor in the progression of airway inflammation.
Citation
Citation: Soleimanifar N, Assadiasl S, Kalateh E, et al. Circulating exosomes and ambient air pollution exposure in COPD. Chronic Obstr Pulm Dis. 2023; 10(4): 412-421. doi: http://dx.doi.org/10.15326/jcopdf.2023.0400
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