|
Jeffrey L. Curtis, MD1,2,3* Lori A. Bateman, MS4* Susan Murray, ScD5 David J. Couper, PhD4 Wassim W. Labaki, MD, MS1 Christine M. Freeman, PhD1,3,6 Kelly B. Arnold, PhD7 Stephanie A. Christenson, MD, MAS8 Neil E. Alexis, PhD9 Mehmet Kesimer, PhD10 Richard C. Boucher, MD10 Robert J. Kaner, MD11 Igor Barjaktarevic, MD, PhD12 Christopher B. Cooper, MD, PhD12 Eric A. Hoffman, PhD13 R. Graham Barr, MD, DrPH14 Eugene R. Bleecker, MD15 Russell P. Bowler, MD, PhD16 Alejandro Comellas, MD17 Mark T. Dransfield, MD18 Michael B. Freedman, MD19 Nadia N. Hansel, MD, MPH20 Jerry A. Krishnan, MD, PhD19 Nathaniel Marchetti, DO21 Deborah A. Meyers, PhD16 Jill Ohar, MD22 Wanda K. O'Neal, PhD10 Victor E. Ortega, MD, PhD15 Robert Paine, III, MD23 Stephen P. Peters, MD, PhD22 Benjamin M. Smith, MD, MS14 Jadwiga A. Wedzicha, MD24 J. Michael Wells, MD, MPH17 Prescott G. Woodruff, MD, MPH8 MeiLan K. Han, MD, MS1** Fernando J. Martinez, MD, MS11** for the SOURCE Investigators
Author Affiliations
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States
- Medical Service, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, United States
- Graduate Program in Immunology, University of Michigan, Ann Arbor, Michigan, United States
- Collaborative Studies Coordinating Center, Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, United States
- Research Service, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, United States
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States
- Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of California San Francisco, San Francisco, California, United States
- Division of Allergy, Immunology, and Infectious Disease, Department of Pediatrics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- Weill Cornell Medicine, New York-Presbyterian Hospital, New York City, New York, United States
- Division of Pulmonary, Critical Care and Sleep Medicine, University of California Los Angeles, Los Angeles, California, United States
- Department of Radiology, University of Iowa, Iowa City, Iowa, United States
- Department of Medicine and Department of Epidemiology, Columbia University Medical Center, New York City, New York, United States
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Scottsdale, Arizona, United States
- Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colorado, United States
- Department of Medicine, University of Iowa, Iowa City, Iowa, United States
- Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States
- Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago, Chicago, Illinois, United States
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
- Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, United States
- Section of Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University, Winston-Salem, North Carolina, United States
- Division of Respiratory, Critical Care, and Occupational Pulmonary Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, United States
- National Heart and Lung Institute, Imperial College, London, United Kingdom
*Co-first authors
**Co-senior authors
Address correspondence to:
Jeffrey L. Curtis, MD
Pulmonary and Critical Care Medicine Section (506/111G)
VA Ann Arbor Healthcare System
2215 Fuller Road
Ann Arbor, MI 48105
Phone: (734) 925-5568
Email: jlcurtis@umich.edu
Abstract
Background: The biological mechanisms leading some tobacco-exposed individuals to develop early-stage chronic obstructive pulmonary disease (COPD) are poorly understood. This knowledge gap hampers development of disease-modifying agents for this prevalent condition.
Objectives: Accordingly, with National Heart, Lung and Blood Institute support, we initiated the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) Study of Early COPD Progression (SOURCE), a multicenter observational cohort study of younger individuals with a history of cigarette smoking and thus at-risk for, or with, early-stage COPD. Our overall objectives are to identify those who will develop COPD earlier in life, characterize them thoroughly, and by contrasting them to those not developing COPD, define mechanisms of disease progression.
Methods/Discussion: SOURCE utilizes the established SPIROMICS clinical network. Its goal is to enroll n=649 participants, ages 30–55 years, all races/ethnicities, with ≥10 pack-years cigarette smoking, in either Global initiative for chronic Obstructive Lung Disease (GOLD) groups 0–2 or with preserved ratio-impaired spirometry; and an additional n=40 never-smoker controls. Participants undergo baseline and 3-year follow-up visits, each including high-resolution computed tomography, respiratory oscillometry and spirometry (pre- and postbronchodilator administration), exhaled breath condensate (baseline only), and extensive biospecimen collection, including sputum induction. Symptoms, interim health care utilization, and exacerbations are captured every 6 months via follow-up phone calls. An embedded bronchoscopy substudy involving n=100 participants (including all never-smokers) will allow collection of lower airway samples for genetic, epigenetic, genomic, immunological, microbiome, mucin analyses, and basal cell culture.
Conclusion: SOURCE should provide novel insights into the natural history of lung disease in younger individuals with a smoking history, and its biological basis.
Citation
Citation: Curtis JL, Bateman LA, Murray S, et al. Design of the SPIROMICS study of early COPD progression: SOURCE study. Chronic Obstr Pulm Dis. 2024; 11(5): 444-459. doi: http://dx.doi.org/10.15326/jcopdf.2023.0490
|
Qinyao Jia, MS1* Yao Chen, MS2* Qiang Zen, MS3* Shaoping Chen, MS4 Shengming Liu, PhD5 Tao Wang, PhD6 XinQi Yuan, BS7
Author Affiliations
- School of Pharmacy, North Sichuan Medical College, Nanchong, China
- Department of Tuberculosis, Chengdu Public Health Clinical Medical Center, Chengdu, China
- Department of Pulmonary and Critical Care Medicine, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China
- Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, China
- Department of Pulmonary and Critical Care Medicine, University of Chinese Academy of Sciences Shenzhen Hospital, Shenzhen, China
- Department of Pulmonary and Critical Care Medicine, The Fifth People's Hospital of Sichuan Province, Chengdu, China
* These authors contributed equally to this work and should be considered co first authors.
Address correspondence to:
Tao Wang, MD
Department of Pulmonary and Critical Care Medicine
University of Chinese Academy of Sciences Shenzhen Hospital
Shenzhen, China
Email: 4941291@qq.com
XinQi Yuan, BS
Department of Respiratory and Critical Care Medicine
The Fifth People's Hospital of Sichuan Province
Chengdu, China
Email: 178503908@qq.com
Abstract
Background: This present work focused on predicting prognostic outcomes of inpatients developing acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and enhancing patient monitoring and treatment by using objective clinical indicators.
Methods: The present retrospective study enrolled 322 AECOPD patients. Registry data downloaded based on the chronic obstructive pulmonary disease (COPD) Pay-for-Performance Program database from January 2012 to December 2018 were used to check whether the enrolled patients were eligible. Our primary and secondary outcomes were intensive care unit (ICU) admission and in-hospital mortality, respectively. The best feature subset was chosen by recursive feature elimination. Moreover, 7 machine learning (ML) models were trained for forecasting ICU admission among AECOPD patients, and the model with the most excellent performance was used.
Results: According to our findings, a random forest (RF) model showed superb discrimination performance, and the values of area under the receiver operating characteristic curve were 0.973 and 0.828 in training and test cohorts, separately. Additionally, according to decision curve analysis, the net benefit of the RF model was higher when differentiating patients with a high risk of ICU admission at a <0.55 threshold probability. Moreover, the ML-based prediction model was also constructed to predict in-hospital mortality, and it showed excellent calibration and discrimination capacities.
Conclusions: The ML model was highly accurate in assessing the ICU admission and in-hospital mortality risk for AECOPD cases. Maintenance of model interpretability helped effectively provide accurate and lucid risk prediction of different individuals.
Citation
Citation: Jia Q, Chen Y, Zen Q, et al. Development and validation of machine learning-based models for prediction of intensive care unit admission and in-hospital mortality in patients with acute exacerbations of chronic obstructive pulmonary disease. Chronic Obstr Pulm Dis. 2024; 11(5): 460-471. doi: http://dx.doi.org/10.15326/jcopdf.2023.0446
|
Jamuna K. Krishnan, MD, MBA, Msc1 Fernando J. Martinez, MD1 Pablo Altman, MD, MBA2* Ver Luanni F. Bilano, PhD3 Edward Khokhlovich, MSc4 Raymond Przybysz, PhD2 Helene Karcher, PhD5* Matthias Schoenberger, PhD5
Author Affiliations
- Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York City, New York, United States
- Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States
- Novartis Pharmaceuticals UK Ltd, London, United Kingdom
- Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts, United States
- Novartis Pharma AG, Basel, Switzerland
* at the time the study was completed
Address correspondence to:
Jamuna K. Krishnan, MD, MBA, MSc
Division of Pulmonary and Critical Care Medicine
Joan and Sanford I. Weill Department of Medicine
Weill Cornell Medicine
New York, New York
Phone: (646) 962-2333
Email: jkk9002@med.cornell.edu
Fernando J. Martinez, MD
Division of Pulmonary and Critical Care Medicine
Joan and Sanford I. Weill Department of Medicine
Weill Cornell Medicine
New York, New York
Phone: (646) 962-2333
Email: fjm2003@med.cornell.edu
Abstract
Background: Patients with chronic obstructive pulmonary disease (COPD) often develop other morbidities, suggesting a systemic component to this disease. This retrospective noninterventional cohort study investigated relationships between multimorbidities in COPD and their impact on COPD exacerbations and COPD-related health care resource utilization (HCRU) using real-world evidence from Optum’s de-identified Clinformatics® Data Mart Database.
Methods: Demographic and clinical characteristics were assessed. Overall comorbidity burden and proportion of individuals with gastroesophageal reflux disease (GERD), diabetes, or osteoporosis/osteopenia were compared in age-matched COPD versus non-COPD cohorts using descriptive statistics. COPD exacerbations and COPD-related HCRU (hospitalizations and emergency department visits) were compared between age-matched cohorts of COPD patients with and without specific common morbidities (GERD, diabetes, and osteoporosis/osteopenia). Additional weight-matching was performed for matched cohorts of COPD patients with and without diabetes, and with and without osteoporosis/osteopenia. The follow-up period was 5 years.
Results: Age-matched cohorts with and without COPD each comprised 158,106 patients. Morbidities were more common in the COPD cohort than the cohort without COPD (GERD: 44.9% versus 27.8%; diabetes: 40.8% versus 31.1%; osteoporosis/osteopenia: 18.8% versus 14.1%, respectively). Compared with matched cohorts with COPD only, cohorts of COPD patients with either GERD, diabetes, or osteoporosis/osteopenia experienced increased risk of severe exacerbations (odds ratio [OR]=1.819, OR=1.119, and OR=1.373, respectively), moderate exacerbations (OR=1.699, OR=1.102, and OR=1.322, respectively), or any exacerbations (OR=1.848, OR=1.099, and OR=1.384, respectively, p<0.001 for all comparisons) and increased risk of COPD-related HCRU (emergency department visits: OR=1.983, OR=1.098, and OR=1.343, respectively; hospitalization visits: OR=2.222, OR=1.26, and OR=1.368, respectively; p<0.001 for all comparisons).
Conclusions: These real-world data confirm that GERD, diabetes, and osteoporosis are common morbidities in patients with COPD and, moreover, that they affect frequency of exacerbation and HCRU. Determining and addressing the mechanisms behind the systemic effects of COPD may be beneficial for COPD patients and may also help reduce COPD exacerbations.
Citation
Citation: Krishnan JK, Martinez FJ, Altman P, et al. Multimorbidities in COPD are associated with increased exacerbations and health care resource utilization in real-world patients from a U.S. database. Chronic Obstr Pulm Dis. 2024; 11(5): 472-481. doi: http://dx.doi.org/10.15326/jcopdf.2024.0515
|
Xiaolu Chen, MM1 Liping Chen, MM1 Guanying Chen, MM1 Jiapei Lv, MM1 Jincong Wang, MM1 Wanjun Yu, MD1 Huaying Wang, MD1
Author Affiliations
- Department of Respiratory and Critical Care, The Affiliated People's Hospital of Ningbo University, Yinzhou People’s Hospital, Ningbo, China
Address correspondence to:
Huaying Wang, MD
Department of Respiratory and Critical Care
The Affiliated People's Hospital of Ningbo University
Yinzhou People’s Hospital
No. 251 Baizhang East Road
Ningbo 315040, China
Phone: 86-13967810430
Email: yingmeire@163.com
Abstract
Background: The interactions between fibroblasts and bronchial epithelial cells play important roles in the development of chronic obstructive pulmonary disease (COPD). Interleukin (IL)-17A triggers the activation of fibroblasts and the secretion of inflammatory mediators, which promotes epithelial-mesenchymal transition (EMT) in bronchial epithelial cells. Fibroblasts secrete C-X-C motif chemokine ligand 12 (CXCL12), which specifically binds to its receptor, C-X-C motif chemokine receptor 4 (CXCR4) to mediate inflammatory responses. This study aims to investigate IL-17A- and CXCL12-induced airway remodeling.
Methods: Primary lung fibroblasts were isolated from human and murine lung tissue for the in vitro experiments, and a mouse model of cigarette smoke (CS)-induced COPD was established for the in vivo experiments. The results were analyzed using a one-way analysis of variance and Tukey’s test or Bonferroni’s test for the post-hoc test. A p-value < 0.05 was considered statistically significant.
Results: Through in vitro experiments, we found that IL-17A-activated primary lung fibroblasts secreted CXCL12 and stimulated EMT in bronchial epithelial cells. However, these effects could be blocked by neutralizing IL-17A or CXCL12. In vivo, an anti-IL-17A antibody or a CXCR4 antagonist could reverse the degree of EMT in the lungs of the COPD mouse model. The IL-17A-induced EMT and increased CXCL12 expression occurred via extracellular signal-regulated kinase (ERK)/phosphorylated-ERK pathways.
Conclusions: This study showed that exposure of mice to CS and IL-17A stimulation upregulated CXCL12 expression and induced EMT by activating the ERK signaling pathway. These data offer a novel perspective regarding the molecular mechanism of CXCL12/CXCR4 signaling in IL-17A-induced EMT related to airway remodeling.
Citation
Citation: Chen X, Chen L, Chen G, et al. Interleukin-17A promotes airway remodeling in chronic obstructive pulmonary disease by activating C-X-C motif chemokine ligand 12 secreted by lung fibroblasts. Chronic Obstr Pulm Dis. 2024; 11(5): 482-495. doi: http://dx.doi.org/10.15326/jcopdf.2024.0495
|
Ashraf Fawzy, MD, MPH1 Jing Gennie Wang, MD2 James G. Krings, MD, MSCI3 Jiaxian He, MS4 Obiageli Offor, MD, MPH1 Michelle N. Eakin, PhD1 Janet T. Holbrook, PhD4 Robert A. Wise, MD1
Author Affiliations
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, United States
- Division of Pulmonary, Critical Care, and Sleep Medicine, Ohio State University, Columbus, Ohio, United States
- Division of Pulmonary and Critical Care Medicine, Washington University in St. Louis, St. Louis, Missouri, United States
- Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, United States
Address correspondence to:
Robert A. Wise, MD
Division of Pulmonary and Critical Care Medicine
Johns Hopkins University
5501 Hopkins Bayview Circle
Baltimore, MD 21224
Email: rwise@jhmi.edu
Abstract
Background: Social distancing early in the COVID-19 pandemic helped mitigate viral spread and protect vulnerable populations. Broad availability of vaccines allowed social re-integration, but effects on mental health, social determinants of health, and attitudes among individuals with chronic obstructive pulmonary disease (COPD), who are high risk for adverse outcomes following COVID-19 infection, are unknown.
Methods: Participants in the Losartan Effects on Emphysema Progression trial were recruited into an ancillary study from May to November 2020. Study coordinators administered telephone questionnaires to evaluate respiratory symptoms (COPD Assessment Test [CAT]), anxiety (Generalized Anxiety Disorder-7 [GAD-7]) and depressive (Patient Health Questionnaire [PHQ-8]) symptoms, social isolation, instrumental support, and attitudes and actions related to the COVID-19 pandemic. Generalized estimating equation models evaluated changes in patient-reported scores from the period before vaccine availability (prevaccine, May to December 2020) to the postvaccine period (May 2021 to September 2022).
Results: Of 157 enrolled participants, 138 were interviewed during both periods. Compared with the prevaccine period, severe respiratory symptoms (CAT>20) were higher in the postvaccine period (odds ratio [OR] 1.36, 95% confidence interval [CI] 95%: 1.00–1.85), as were moderate anxiety symptoms (GAD-7≥10; OR 1.65, 95%CI: 1.11–2.46) and moderate depressive symptoms (PHQ-8≥10; OR 1.77, 95%CI: 1.22–2.55). Social isolation improved, though not significantly, and instrumental support was unchanged. In the postvaccine period compliance with COVID-19 mitigation strategies remained high and governmental health care entities were viewed as trustworthy by fewer respondents.
Conclusions: Despite a trend towards less social isolation following broad availability of COVID-19 vaccines, individuals with COPD reported worse symptoms, and greater anxiety and depressive symptoms compared to the prevaccine period.
Citation
Citation: Fawzy A, Wang JG, Krings JG, et al. Impact of COVID-19 vaccine rollout on mental health, social determinants of health, and attitudes among individuals with COPD. Chronic Obstr Pulm Dis. 2024; 11(5): 496-506. doi: http://dx.doi.org/10.15326/jcopdf.2024.0537
|
Joshua De Soyza, BMBS1 Paul Ellis, PhD1 Michael Newnham, PhD1 Lloyd Rickard, MBBS2 Alice M. Turner, PhD1
Author Affiliations
- University of Birmingham, Institute of Applied Health Research, Birmingham, United Kingdom
- University Hospitals Birmingham, Edgbaston, United Kingdom
Abstract
Introduction: Bronchiectasis occurs in patients with alpha-1 antitrypsin deficiency (AATD), but it is unknown whether an association exists independently of chronic obstructive pulmonary disease (COPD). We assessed whether bronchiectasis was associated with COPD in our cohort, and whether it has clinical significance for lung function decline, exacerbation rate, or symptoms.
Study Design and Methods: PiZZ, PiSZ, and PiMZ patients from the Birmingham AATD Research Database were studied. Demographics were recorded, along with the outcomes of symptoms, forced expiratory volume in 1 second (FEV1), transfer factor of carbon monoxide (TLCO), carbon monoxide transfer coefficient (KCO), and annualized exacerbation rate. Lung function decline was calculated for those with ≥3 measurements. Multivariate regression analyses were conducted to assess for associations of bronchiectasis with each outcome. A further binomial logistic regression model assessed for predictors of bronchiectasis diagnosis, including COPD. Those with alternative bronchiectasis causes were excluded from statistical models.
Results: A total of 1290 patients were eligible. PiZZ patients with bronchiectasis were older at presentation (54 versus 49 years, p<0.001), less likely to have smoked (65% versus 76.1%, p=0.001), and had higher modified Medical Research Council scores (mMRC) (mMRC 2 versus 0 odds ratio [OR] 1.97, 95% constant interval [CI] 1.20–3.25, p=0.008; mMRC 3 versus 0 OR 2.58 95% CI 1.59–4.19, p<0.001; mMRC 4 versus 0 OR 2.2 95% CI 1.23–3.92; p=0.008) than those without. The OR of bronchiectasis diagnosis was not associated with COPD diagnosis in any phenotype. Bronchiectasis was associated with lower serum alpha-1 antitrypsin levels in PiZZ patients (p=0.012). Bronchiectasis was not associated with a difference in FEV1 percentage predicted (pp)/year decline, KCO pp/year, TLCO pp/year decline, or exacerbation rate in multivariate analysis.
Conclusions: Bronchiectasis exists in a significant minority of AATD patients independently of COPD and is associated with more severe shortness of breath. Appropriate treatment of bronchiectasis in AATD is essential.
Citation
Citation: De Soyza J, Ellis P, Newnham M, Rickard L, Turner AM. Bronchiectasis occurs independently of chronic obstructive pulmonary disease in alpha-1 antitrypsin deficiency. Chronic Obstr Pulm Dis. 2024; 11(5): 507-514. doi: http://dx.doi.org/10.15326/jcopdf.2024.0526
|
Thomas Brazeal, PharmD1 Leanne Kaye, PhD, MPH, RD2 Vy Vuong, MS2 Jade Le, PharmD1 Zachary Peris1 Meredith A Barrett, PhD2
Author Affiliations
- Desert Oasis Healthcare, Palm Springs, California, United States
- ResMed Science Center, San Diego, California, United States
Address correspondence to:
Leanne Kaye, PhD, MPH, RD
ResMed Science Center
San Diego, CA
Phone: 1 (800) 424-0737
Email: leanne.kaye@resmed.com
Abstract
Introduction: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that adds a significant economic burden to the health care system in the United States. Digital platforms integrated into clinical workflows have demonstrated success in improving patient outcomes in COPD, but few studies have explored the impact of an integrated digital and clinical approach on drivers of direct health care costs (COPD-related prescriptions, emergency department [ED] visits, and hospitalizations) in a real-world setting.
Methods: We conducted a 6-month retrospective matched control analysis to assess the impact of a digital quality improvement (QI) program delivered by clinical pharmacists on health care resource utilization among people living with COPD.
Results: Compared to matched controls at 6 months, participants in the digital QI program had a 66.7% relative reduction in COPD-related ED visits and hospitalizations (0.04±0.19 versus 0.12±0.44, p=0.044), as well as a 47% reduction in all-cause ED visits and hospitalizations (0.25±0.63 versus 0.47±1.09, p=0.059). Participants in the digital QI program also had higher rates of COPD-related prescription fills for antibiotics (0.43±0.93 versus 0.35±0.74, p=0.881) and oral corticosteroids (0.56±1.02 versus 0.36±0.91, p=0.045), as well as a greater number of COPD-related nonacute urgent care visits compared to matched controls (0.3±0.63 versus 0.14±0.44, p=0.027).
Conclusion: Digital health platforms integrated into a virtual clinical pharmacist workflow can help reduce costly COPD-related ED visits and hospitalizations, and shift utilization to less acute care. Care models integrating digital platforms may also offer a scalable approach to managing COPD and should be explored in different clinical settings.
Citation
Citation: Brazeal T, Kaye L, Vuong V, Le J, Peris Z, Barrett MA. Reducing health care resource utilization in COPD: a retrospective matched control analysis of a digital quality improvement program. Chronic Obstr Pulm Dis. 2024; 11(5): 515-523. doi: http://dx.doi.org/10.15326/jcopdf.2024.0532
|
|