Chronic Obstructive Pulmonary Diseases:Journal of the COPD Foundation

Volume 9, Issue 2 - 2022

Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation is an open access, peer-reviewed medical/scientific journal dedicated to publishing original research, reviews, and communications related to COPD. Articles are published online as quickly as possible following peer review and editorial acceptance and then aggregated into quarterly issues, and made available to the COPD medical/research community at no charge. The Journal is indexed by PubMed, PubMed Central, Scopus and Web of Science.

Original Research:

Forced Expiratory Flow at 25%-75% Links COPD Physiology to Emphysema and Disease Severity in the SPIROMICS Cohort

Bonnie E. Ronish, MD1 David J. Couper, PhD2 Igor Z. Barjaktarevic, MD, PhD3 Christopher B. Cooper, MD3, 4 Richard E. Kanner, MD1 Cheryl S. Pirozzi, MD, MS1 Victor Kim, MD5 James M. Wells, MD6 MeiLan K. Han, MD, MS7 Prescott G. Woodruff, MD, MPH8 Victor E. Ortega, MD, PhD9 Stephen P. Peters, MD, PhD10 Eric A. Hoffman, PhD11 Russell G. Buhr, MD, PhD3,12 Brett A. Dolezal, PhD3 Donald P. Tashkin, MD3 Theodore G. Liou, MD1 Lori A. Bateman, MS 2 Joyce D. Schroeder, MD13 Fernando J. Martinez, MD, MS14 R. Graham Barr, MD, PhD15 Nadia N. Hansel, MD, MPH16 Alejandro P. Comellas, MD17 Stephen I. Rennard, MD18 Mehrdad Arjomandi, MD8,19 Robert Paine III, MD1

Author Affiliations

  1. Division of Respiratory, Critical Care, and Occupational Pulmonary Medicine, University of Utah, Salt Lake City, Utah, United States
  2. Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  3. Division of Pulmonary and Critical Care, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States
  4. Department of Physiology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States
  5. Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine, Temple University Hospital, Philadelphia, Pennsylvania, United States
  6. Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States
  7. Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, United States
  8. Department of Medicine, University of California San Francisco, San Francisco, California, United States
  9. Division of Internal Medicine, Wake Forest School of Medicine, Winston Salem, North Carolina, United States
  10. Division of Internal Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina, United States
  11. Division of Physiologic Imaging, Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States
  12. Center for the Study of Healthcare Innovation, Implementation, and Policy, VA Health Services Research and Development, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California, United States
  13. Division of Radiology and Imaging Sciences, University of Utah, Salt Lake City, Utah, United States
  14. Division of Pulmonary and Critical Care, Weill Cornell Medicine, New York, New York, United States
  15. Department of Internal Medicine, Columbia University, New York, New York, United States
  16. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  17. Division of Pulmonary, Critical Care and Occupational Medicine, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States
  18. Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, United States
  19. San Francisco Veterans Affairs Healthcare System, San Francisco, California, United States

Address correspondence to:

Robert Paine III, MD
26 N 1900 E
Salt Lake City, UT 84132
Email: Robert.paine@hsc.utah.edu
Phone: 801-597-6821

Abstract

Background: Forced expiratory volume in 1 second (FEV1) is central to the diagnosis of chronic obstructive pulmonary disease (COPD) but is imprecise in classifying disease burden. We examined the potential of the maximal mid-expiratory flow rate (forced expiratory flow rate between 25% and 75% [FEF25%-75%]) as an additional tool for characterizing pathophysiology in COPD.

Objective: To determine whether FEF25%-75% helps predict clinical and radiographic abnormalities in COPD.

Study Design and Methods: The SubPopulations and InteRediate Outcome Measures In COPD Study (SPIROMICS) enrolled a prospective cohort of 2978 nonsmokers and ever-smokers, with and without COPD, to identify phenotypes and intermediate markers of disease progression. We used baseline data from 2771 ever-smokers from the SPIROMICS cohort to identify associations between percent predicted FEF25%-75% (%predFEF25%-75%) and both clinical markers and computed tomography (CT) findings of smoking-related lung disease.

Results: Lower %predFEF25-75% was associated with more severe disease, manifested radiographically by increased functional small airways disease, emphysema (most notably with homogeneous distribution), CT-measured residual volume, total lung capacity (TLC), and airway wall thickness, and clinically by increased symptoms, decreased 6-minute walk distance, and increased bronchodilator responsiveness (BDR). A lower %predFEF25-75% remained significantly associated with increased emphysema, functional small airways disease, TLC, and BDR after adjustment for FEV1 or forced vital capacity (FVC).

Interpretation: The %predFEF25-75% provides additional information about disease manifestation beyond FEV1. These associations may reflect loss of elastic recoil and air trapping from emphysema and intrinsic small airways disease. Thus, %predFEF25-75% helps link the anatomic pathology and deranged physiology of COPD.

Citation

Citation: Ronish BE, Couper DJ, Barjaktarevic IZ, et al. Forced expiratory flow at 25%-75% links COPD physiology to emphysema and disease severity in the SPIROMICS cohort. Chronic Obstr Pulm Dis. 2022; 9(2): 111-121. doi: http://dx.doi.org/10.15326/jcopdf.2021.0241

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Disparities in Hospitalized Chronic Obstructive Pulmonary Disease Exacerbations Between American Indians and Non-Hispanic Whites

Huimin Wu, MD, MPH1 Dorothy A. Rhoades, MD, MPH2 Sixia Chen, PhD3 Matt Slief, MD4 Carla A. Guy, BS3 Adam Warren, BS3 Brent Brown, MD1

Author Affiliations

  1. Pulmonary, Critical Care and Sleep Medicine Section, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  2. General Internal Medicine, College of Medicine, and Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  3. Biostatistics and Epidemiology, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  4. College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States

Address correspondence to:

Huimin Wu, MD, MPH
Phone: 405-271-6173
Email: Huimin-Wu@ouhsc.edu

Abstract

Background: The prevalence of chronic obstructive pulmonary disease (COPD) is high in American Indian (AI) populations, as are diabetes and obesity, which are common COPD comorbidities. However, COPD research among AI populations is limited.

Study Design and Methods: We conducted a retrospective study to investigate potential health disparities and risk factors among AI and non-Hispanic White (NHW) patients with COPD exacerbations hospitalized at the University of Oklahoma Medical Center between July 2001 and June 2020. Demographics, clinical variables, and outcomes were collected.

Results: A total of 76 AI patients and 304 NHW patients were included. AI patients had more comorbidities than did NHW patients (4.3 versus.3.1, p<0.001). In multiple variable analyses, AI race was associated with higher odds of needing intensive care unit (ICU) care ( odds ratio [OR], 2.37, 95% confidence interval [CI], 1.36­–4.16, p=0.002) and invasive mechanical ventilator use (OR, 2.75, 95% CI, 1.42–5.29, p=0.002). AI race was also associated with longer ICU stays compared with NHWs (OR, 1.43, 95% CI, 1.18­–1.73, p<0.001). The average number of days on mechanical ventilator support increased by 137.3% for an AI patient compared to an NHW patient (p<0.001). AI race was not associated with discharge to other health facilities (OR, 0.98, 95% CI, 0.52–1.83, p=0.944).

Interpretation: AI patients were more likely than NHW patients to need ICU care and ventilator support, have longer ICU stays, and more days on mechanical ventilator support. More studies are needed to identify reasons for these disparities and effective interventions to reduce them.

Citation

Citation: Wu H, Rhoades DA, Chen S, et al. Disparities in hospitalized chronic obstructive pulmonary disease exacerbations between American Indians and non-Hispanic Whites. Chronic Obstr Pulm Dis. 2022; 9(2): 122-134. doi: http://dx.doi.org/10.15326/jcopdf.2021.0246

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Trends and Characteristics of Global Initiative for Chronic Obstructive Lung Disease Guidelines-Discordant Prescribing of Triple Therapy Among Patients with COPD

Surya P. Bhatt, MD, MSPH1 Cori Blauer-Peterson, MPH2 Erin K. Buysman, MS2 Lindsay G.S. Bengtson, PhD, MPH2 Swetha R. Palli, MS3

Author Affiliations

  1. Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States
  2. Health Economics and Outcomes Research, Optum, Eden Prairie, Minnesota, United States
  3. Value Demonstration Team, Boehringer Ingelheim, Ridgefield, Connecticut, United States

Address correspondence to:

Swetha R. Palli, MS
E-mail: swetha.palli@boehringer-ingelheim.com
Phone: (203)798-4460

Abstract

Background: Triple therapy (long-acting muscarinic antagonist [LAMA] plus long-acting beta2-agonist [LABA] plus inhaled corticosteroid [ICS]) is recommended by the Global initiative for chronic Obstructive Lung Disease (GOLD) for moderate-to-severe chronic obstructive pulmonary disease (COPD) with a history of frequent and/or severe exacerbation(s) and dyspnea while using dual bronchodilators. However, many patients receive triple therapy contrary to these recommendations. This study describes factors associated with GOLD-discordant triple therapy initiation.

Methods: This retrospective analysis included patients aged 40 and above, with ≥1 COPD diagnosis, who initiated triple therapy (initiation=index date) during the period January 1, 2014 to December 31, 2018 and had ≥12 months pre-index continuous enrollment (baseline). Triple therapy comprised ≥30 days of overlapping LAMA, LABA, and ICS treatments (open triple therapy), or single-inhaler fluticasone furoate/umeclidinium/vilanterol (closed triple therapy). Cohorts were defined based on the absence of baseline maintenance medication use (“maintenance-naïve”), and/or exacerbations (“exacerbation-discordant”), or “dual-discordant” (discordant on both measures). All triple therapy initiators, overall and for each cohort, were described, and predictors of GOLD-discordant triple therapy initiation were identified.

Results: Among 21,711 triple therapy initiators, 34.4% were maintenance-naïve, 61.9% exacerbation-discordant, and 22.2% dual-discordant. Triple therapy initiation appeared to increase during the period 2016 to 2018. In 2018 alone, 31.9% and 58.3% of open triple therapy patients were maintenance-naïve and exacerbation-discordant, respectively, versus 37.6% and 64.4% of closed triple therapy patients. Closed triple therapy initiators had 1.65 times greater risk of dual discordance than open triple therapy initiators. Exacerbation-discordant patients initiating closed triple therapy were 1.61 times more likely to be maintenance-naïve than those initiating open triple therapy.

Conclusion: A substantial proportion of COPD patients initiating triple therapy do not meet GOLD recommendations regarding exacerbation history and/or prior maintenance therapy. Compared with open triple therapy, closed triple therapy initiators were more likely to be dual discordant.

Citation

Citation: Bhatt SP, Blauer-Peterson C, Buysman EK, Bengston LGS, Palli SR. Trends and characteristics of Global Initiative for Chronic Obstructive Lung Disease guidelines-discordant prescribing of triple therapy among patients with COPD. Chronic Obstr Pulm Dis. 2022; 9(2): 135-153. doi: http://dx.doi.org/10.15326/jcopdf.2021.0256

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Computed Tomography Features of Lung Structure Have Utility for Differentiating Malignant and Benign Pulmonary Nodules

Johanna M. Uthoff, PhD1,2,3 Sarah L. Mott, MS3 Jared Larson, BS1 Christine M. Neslund-Dudas, PhD4,5 Ann G. Schwartz, PhD, MPH6 Jessica C. Sieren, PhD1,2,3 and the COPDGene® Investigators

Author Affiliations

  1. Department of Radiology, University of Iowa, Iowa City, Iowa, United States
  2. Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, United States
  3. Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa, United States
  4. Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, United States
  5. Henry Ford Cancer Institute, Henry Ford Health System, Detroit, Michigan, United States
  6. Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, United States

Address correspondence to:

Jessica C. Sieren, PhD
University of Iowa
Department of Radiology
200 Hawkins Drive, CC704GH
Iowa City, IA 52242
Phone: (319) 356-1407
Email: Jessica-sieren@uiowa.edu

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a known comorbidity for lung cancer independent of smoking history. Quantitative computed tomography (qCT) imaging features related to COPD have shown promise in the assessment of lung cancer risk. We hypothesize that qCT features from the lung, lobe, and airway tree related to the location of the pulmonary nodule can be used to provide informative malignancy risk assessment.

Methods: A total of 183 qCT features were extracted from 278 individuals with a solitary pulmonary nodule of known diagnosis (71 malignant, 207 benign). These included histogram and airway characteristics of the lungs, lobe, and segmental paths. Performances of the least absolute shrinkage and selection operator (LASSO) regression analysis and an ensemble of neural networks (ENN) were compared for feature set selection and classification on a testing cohort of 49 additional individuals (15 malignant, 34 benign).

Results: The LASSO and ENN methods produced different feature sets for classification with LASSO selecting fewer qCT features (7) than the ENN (17). The LASSO model with the highest performing training area under the curve (AUC) (0.80) incorporated automatically extracted features and reader-measured nodule diameter with a testing AUC of 0.62. The ENN model with the highest performing AUC (0.77) also incorporated qCT and reader diameter but maintained higher testing performance AUC (0.79).

Conclusions: Automatically extracted qCT imaging features of the lung can be informative of the differentiation between individuals with malignant pulmonary nodules and those with benign pulmonary nodules, without requiring nodule segmentation and analysis.

Citation

Citation: Uthoff JM, Mott SL, Larson J, et al; the COPDGene Investigators. Computed tomography features of lung structure have utility for differentiating malignant and benign pulmonary nodules. Chronic Obstr Pulm Dis. 2022; 9(2): 154-164. doi: http://dx.doi.org/10.15326/jcopdf.2021.0271

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Treatable Traits in Misdiagnosed Chronic Obstructive Pulmonary Disease: Data from the Akershus Cardiac Examination 1950 Study

Nina Faksvåg Caspersen, MD1,2 Vidar Søyseth, MD,PhD1,2 Magnus Nakrem Lyngbakken, MD, PhD1,2 Trygve Berge, MD, PhD2,3 Inger Ariansen, MD, PhD4 Arnljot Tveit, MD, PhD2,3 Helge Røsjø, MD, PhD2,5 Gunnar Einvik, MD, PhD1,2

Author Affiliations

  1. Division of Medicine, Akershus University Hospital, Lørenskog, Norway
  2. Institute of Clinical Medicine, University of Oslo, Oslo, Norway
  3. Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Gjettum, Norway
  4. Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway
  5. Division for Research and Innovation, Akershus University Hospital, Lørenskog, Norway

Address correspondence to:

Gunnar Einvik, MD, PhD
Department of Pulmonary Medicine
Division of Medicine
Akershus University Hospital, Pb 1000
1470 Lørenskog, Norway
E-mail: gunnar.einvik@medisin.uio.no
Phone +47 41104542

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is often misdiagnosed. We aimed to estimate the prevalence of misdiagnosed COPD in middle-aged Norwegians, and to assess potentially treatable clinical traits in over- and undiagnosed individuals.

Methods and Findings: The Akershus Cardiac Examination (ACE) 1950 Study is a population-based study of the 1950 birth cohort of Akershus county including 3706 participants aged 62-65 years at baseline. COPD was defined as a forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio < lower limit of normal (LLN). Misdiagnosed COPD was defined according to self-reported COPD.

A total of 259 (7.1%) participants had spirometry confirmed COPD. Of these, only 72 (28%) reported having COPD, thus 187 (72%) were undiagnosed. A total of 92 (2.5%) of the 164 particpants who reported having COPD had an FEV1/FVC ratio ≥ LLN and were overdiagnosed. They had lower lung function, and more respiratory symptoms, self-reported asthma, eosinophils, and sleep apnea than other non-COPD participants . The main predictor of being overdiagnosed was overweight. Spirometry in participants reporting wheezing or cough and current smokers or participants with ≥20 tobacco pack-year history would have identified 85% of the undiagnosed cases.

Conclusion: Both over- and underdiagnosis of COPD is frequent. Undiagnosed individuals have better lung function and less symptoms, but similar prevalence of comorbidities and systemic inflammation. Overdiagnosed individuals have treatable traits including asthma, eosinophilic inflammation, and sleep apnea. The main predictor of being overdiagnosed was being overweight.

Citation

Citation: Caspersen NF, Soyseth V, Lyngbakken MN, et al. Treatable traits in misdiagnosed chronic obstructive pulmonary disease: data from the Akershus Cardiac Examination 1950 study. Chronic Obstr Pulm Dis. 2022; 9(2): 165-180. doi: http://dx.doi.org/10.15326/jcopdf.2021.0265

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Current-Smoking-Related COPD or COPD With Acute Exacerbation is Associated With Poorer Survival Following Oral Cavity Squamous Cell Carcinoma Surgery

Jiaqiang Zhang, MD, PhD1* Wei-Chun Lin, MD2* Kuo-Chin Chiu, MD3 Szu-Yuan Wu, MD, MPH, PhD4,5,6,7,8,9
*These authors have contributed equally to this study (coauthors).

Author Affiliations

  1. Department of Anesthesiology and Perioperative Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China
  2. Division of Chest, Department of Internal Medicine, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan
  3. Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan
  4. Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan
  5. Division of Radiation Oncology, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan
  6. Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan
  7. Cancer Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan
  8. Graduate Institute of Business Administration, Fu Jen Catholic University, Taipei, Taiwan
  9. Centers for Regional Anesthesia and Pain Medicine, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

Address correspondence to:

Szu-Yuan Wu, MD, MPH, PhD & Kuo-Chin Chiu, MD
No. 83, Nanchang St.
Luodong Township
Yilan County 265, Taiwan
Email: szuyuanwu5399@gmail.com

Abstract

Background: The survival effect of smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) before surgery on patients with oral cavity squamous cell carcinoma (OCSCC) is unclear.

Methods: Using the Taiwan Cancer Registry Database, we enrolled patients with OCSCC (pathologic stages I–IVB) receiving surgery. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into 2 groups by using propensity score matching based on the pre-existing COPD status (≤1 year before surgery) to compare overall survival outcomes: Group 1 (never smokers without COPD) and Group 2 (current smokers with COPD).

Results: In multivariate Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval [CI]) of all-cause mortality in Group 2 compared with Group 1 was 1.07 (1.02–1.16, P = 0.041). The aHR (95% CIs) of all-cause mortality for ≥1 hospitalizations for COPDAE within 1 year before surgery for patients with OCSCC was 1.31 (1.02–1.64; P = 0.011) compared with no COPDAE in patients with OCSCC receiving surgery. Among patients with OCSCC undergoing curative surgery, current smokers with smoking-related COPD demonstrated poorer survival outcomes than did nonsmokers without COPD, for both OCSCC death and all-cause mortality. Hospitalization for COPDAE within 1 year before surgery was found to be an independent risk factor for overall survival in these patients with OCSCC.

Conclusion: Prevention of COPD progression to COPDAE may lead to an increase in overall survival in patients with OCSCC receiving curative surgery.

Citation

Citation: Zhang J, Lin W-C, Chiu K-C, Wu S-Y. Current smoking-related COPD or COPD with acute exacerbation is associated with poorer survival following oral cavity squamous cell carcinoma surgery. Chronic Obstr Pulm Dis. 2022; 9(2): 181-194. doi: http://dx.doi.org/10.15326/jcopdf.2022.0286

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Characterizing COPD Symptom Variability in the Stable State Utilizing the Evaluating Respiratory Symptoms in COPD Instrument

Jamuna K. Krishnan, MD, MS1* Kayley M. Ancy, MD2* Clara Oromendia, MS3 Katherine L. Hoffman, MS3 Imaani Easthausen, MS3 Nancy K. Leidy, PhD4 MeiLan K. Han, MD, MS5 Russell P. Bowler, MD, PhD6 Stephanie A. Christenson, MD7 David J. Couper, PhD8 Gerard J. Criner, MD9 Jeffrey L. Curtis, MD5,10 Mark T. Dransfield, MD11 Nadia N. Hansel, MD, MPH12 Anand S. Iyer, MD11 Robert Paine III, MD13 Stephen P. Peters, MD, PhD14 Jadwiga A. Wedzicha, MD15 Prescott G. Woodruff, MD, MPH7 Karla V. Ballman, PhD3 Fernando J. Martinez, MD, MS1 for the SPIROMICS Investigators
*Co-first authors, both authors contributed equally to the work.

Author Affiliations

  1. Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, New York, United States
  2. Department of Medicine, Weill Cornell Medicine, New York, New York, United States
  3. Division of Biostatistics, Department of Population Health Sciences, Weill Cornell Medical College, New York, New York, United States
  4. Evidera, Bethesda, Maryland, United States
  5. Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor, Michigan, United States
  6. Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado, United States
  7. Pulmonary and Critical Care, University of California San Francisco, San Francisco, California, United States
  8. University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  9. Pulmonary and Critical Care Medicine, Temple University Hospital, Philadelphia, Pennsylvania, United States
  10. Medical Service, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, United States
  11. Pulmonary, Allergy and Critical Care, University of Alabama at Birmingham, Birmingham, Alabama, United States
  12. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore Maryland, United States
  13. Division of Pulmonary and Critical Care Medicine, Department of Veterans Affairs Medical Center, University of Utah, Salt Lake City, Utah, United States
  14. Section on Pulmonary, Critical Care, Allergy and Immunological Diseases, Wake Forest School of Medicine Medical Center, Winston-Salem, North Carolina, United States
  15. National Heart and Lung Institute, Imperial College London, United Kingdom

Address correspondence to:

Jamuna K. Krishnan, MD
Division of Pulmonary and Critical Care Medicine
Weill Cornell Medicine
1305 York Avenue, Y-1047, Box 96
New York, NY 10021
Phone: 646-962-2333
Email: jkk9002@med.cornell.edu

Abstract

Rationale: It has been suggested that patients with chronic obstructive pulmonary disease (COPD) experience considerable daily respiratory symptom fluctuation. A standardized measure is needed to quantify and understand the implications of day-to-day symptom variability.

Objectives: To compare standard deviation with other statistical measures of symptom variability and identify characteristics of individuals with higher symptom variability.

Methods: Individuals in the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) Exacerbations sub-study completed an Evaluating Respiratory Symptoms in COPD (E-RS) daily questionnaire. We calculated within-subject standard deviation (WS-SD) for each patient at week 0 and correlated this with measurements obtained 4 weeks later using Pearson’s r and Bland Altman plots. Median WS-SD value dichotomized participants into higher versus lower variability groups. Association between WS-SD and exacerbation risk during 4 follow-up weeks was explored.

Measurements and Main Results: Diary completion rates were sufficient in 140 (68%) of 205 sub-study participants. Reproducibility (r) of the WS-SD metric from baseline to week 4 was 0.32. Higher variability participants had higher St George’s Respiratory Questionnaire (SGRQ) scores (47.3 ± 20.3 versus 39.6 ± 21.5, p=.04) than lower variability participants. Exploratory analyses found no relationship between symptom variability and health care resource utilization-defined exacerbations.

Conclusions: WS-SD of the E-RS can be used as a measure of symptom variability in studies of patients with COPD. Patients with higher variability have worse health-related quality of life. WS-SD should be further validated as a measure to understand the implications of symptom variability.

Citation

Citation: Krishnan JK, Ancy KM, Oromendia C, et al. Characterizing COPD symptom variability in the stable state utilizing the Evaluating Respiratory Symptoms in COPD instrument. Chronic Obstr Pulm Dis. 2022; 9(2): 195-208. doi: http://dx.doi.org/10.15326/jcopdf.2021.0263

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Evaluation of COPD Chronic Care Management Collaborative to Reduce Emergency Department and Hospital Revisits Across U.S. Hospitals

Valerie G. Press, MD, MPH1 Kelly Randall, BA2 Amber Hanser, MHA2

Author Affiliations

  1. Section of General Internal Medicine, Department of Medicine, University of Chicago, Chicago, Illinois, United States
  2. Vizient, Inc., Irving, Texas, United States

Address correspondence to:

Valerie Press, MD, MPH
University of Chicago
5841 S Maryland, MC 2007
Chicago, IL 60637
Phone: (773)702-5170
Email: vpress@bsd.uchicago.edu

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is the third-leading cause of early readmissions. The Centers for Medicare and Medicaid instituted a financial penalty for excessive COPD readmissions galvanizing hospitals to implement effective strategies to reduce readmissions. We evaluated a 6-month COPD Chronic Care Management Collaborative to support hospitals to reduce preventable COPD-related revisits.

Methods: Sites were recruited among nearly 300 Vizient, Inc., members. The Collaborative used performance improvement initiatives to assist with implementation of effective strategies. Participants submitted performance data for 2 outcome measures: emergency department (ED) and hospital revisits.

Results: Forty-seven members enrolled (Part I+II: n=33; Part I: n=3; Part II: n=11) of which 23 submitted data (n=23/47). The majority (n=19/23, 83%) reduced rates of COPD-related ED and/or hospital revisits. Among all 23 sites, the change in ED visits went from 11.05% to 10.87%; among 7 sites with reductions in ED visits, the reduction was 12.7% to 9%. Among all 23 sites, there were not reductions in hospital readmissions (18.53% to 18.64%); among 7 sites with reductions, the readmission rate went from 20.1% to 15.6%. The mean reach across 17 hospitals reporting reach for their most successful measure at baseline was 35.2% (SD=26.7%) and for the other 6, reporting reach at follow-up was 73.8%% (SD=18.3%); of note, only 3 sites submitted both baseline and follow-up data.

Conclusions: The Collaborative successfully supported the majority of sites in reducing COPD-related ED and/or hospital revisits using subject matter experts and coaching strategies to support hospitals' implementation of COPD quality improvement interventions.

Citation

Citation: Press VG, Randall K, Hanser A. Evaluation of COPD chronic care management collaborative to reduce emergency department and hospital revisits across U.S. hospitals. Chronic Obstr Pulm Dis. 2022; 9(2): 209-225. doi: http://dx.doi.org/10.15326/jcopdf.2021.0273

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Heart Rate Variability on 10-Second Electrocardiogram and Risk of Acute Exacerbation of COPD: A Secondary Analysis of the BLOCK COPD Trial

David M. MacDonald, MD, MS1,2 Takudzwa Mkorombindo, MD3 Sharon X. Ling, BS4† Selcuk Adabag, MD, MS5 Richard Casaburi, MD, PhD6 John E. Connett, PhD4 Erika S. Helgeson, PhD4 Janos Porszasz, MD, PhD6 Harry B. Rossiter, PhD6 William W. Stringer, MD6 Helen Voelker, BA4 Dongxing Zhao, PhD, MD7 Mark T. Dransfield, MD3 Ken M. Kunisaki, MD, MS1,2

Author Affiliations

  1. Pulmonary Section, Minneapolis VA Health Care System, Minneapolis, Minnesota, United States
  2. Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Minnesota, Minneapolis, Minnesota, United States
  3. Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama, United States
  4. Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota, United States
  5. Cardiology Section, Minneapolis VA Health Care System, Minneapolis, Minnesota, United States
  6. Lundquist Institute for Biomedical Innovation at Harbor–UCLA Medical Center, Torrance, California, United States
  7. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China

† deceased

Address correspondence to:

David MacDonald, MD, MS
Minneapolis VA Health Care System
Pulmonary, Critical Care, and Sleep (111N)
One Veterans Drive
Minneapolis, MN, USA, 55417
Email: macdo147@umn.edu

Abstract

Introduction: Autonomic dysfunction is common in chronic obstructive pulmonary disease (COPD), and worse autonomic function may be a marker of risk for acute exacerbations of COPD (AECOPD). Heart rate variability (HRV) is a measure of autonomic function. Our objective was to test whether lower (worse) HRV is a risk factor for AECOPD.

Methods: We measured standard deviation of normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) on 10-second electrocardiograms (ECGs) performed at screening and day 42 in participants in the Beta Blockers for the Prevention of Acute Exacerbations of COPD trial ( BLOCK-COPD), a placebo-controlled trial of metoprolol for prevention of AECOPD. We used Cox-proportional hazards models to test if these HRV measures were associated with risk of any AECOPD, and separately, hospitalized AECOPD. We tested associations using baseline HRV measures and incorporating HRV measures from day 42 as a time-varying covariate. We also tested for interactions with metoprolol assignment.

Results: Of 532 trial participants, 529 (forced expiratory volume in 1 second [FEV1 ]41 ± 16.3 % predicted) were included in this analysis. We did not find a significant association between HRV measures and risk of AECOPD when all participants were analyzed together. There was a significant interaction between RMSSD and assignment to metoprolol on time to first hospitalized AECOPD; in the placebo group greater RMSSD was associated with a lower risk of hospitalized AECOPD (adjusted hazard ratio0.71, 95% confidence interval: 0.52 to 0.96, per 10 ms increase) but there was no association in the metoprolol group.

Conclusions: Autonomic dysfunction as measured by HRV may be a risk factor for AECOPD. Future studies should analyze longer HRV recordings and their performance in broader samples of people with COPD, including those on beta-blockers.

Citation

Citation: MacDonald DM, Mkorombindo T, Ling SX, et al. Heart rate variability on 10-second electrocardiogram and risk of acute exacerbation of COPD: a secondary analysis of the BLOCK COPD trial. Chronic Obstr Pulm Dis. 2022; 9(2): 226-236. doi: http://dx.doi.org/10.15326/jcopdf.2021.0264

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Review:

Home Non-Invasive Ventilation in COPD: A Global Systematic Review

Janine Dretzke, MSc1 Jingya Wang, PhD1 Mi Yao, MSc1 Naijie Guan, MSc1 Myra Ling2 Erica Zhang2 Deyashini Mukherjee, MBBS3 James Hall, PhD4 Sue Jowett, PhD4 Rahul Mukherjee, MBBS, FRCP5 David J. Moore, PhD1 Alice M. Turner, MBChB, PhD1,5

Author Affiliations

  1. Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
  2. Birmingham Medical School, University of Birmingham, Birmingham, United Kingdom
  3. University Hospitals Coventry and Warwickshire, Coventry, United Kingdom
  4. Health Economics Unit, Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
  5. University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom

Address correspondence to:

Janine Dretzke, MSc
Institute of Applied Health Research
University of Birmingham, B15 2TT
Birmingham, United Kingdom
Phone: +44 (121) 4147850
Email: j.dretzke@bham.ac.uk

Abstract

Background: Uncertainty remains around the benefit of home non-invasive ventilation (NIV) for stable chronic obstructive pulmonary disease (COPD) patients and those with a recent exacerbation (post-hospital). The aim of this systematic review was to: (1) update the evidence base with studies published in any language, including Chinese language studies not indexed in standard medical databases, and (2) explore the impact of additional studies on the evidence base.

Methods: Standard systematic review methodology was used for identifying and appraising studies. Randomized controlled trials (RCTs) and non-randomized studies reporting mortality, hospitalizations, exacerbations, quality of life, adverse events, or adherence were included. Random effects meta-analysis was undertaken for mortality and hospitalizations, with studies sub-grouped by population and study design. Sensitivity analysis was performed to explore the effect of including studies from Western and non-Western countries.

Results: A total of 103 studies were included, substantially more than in previous reviews. There was no significant effect on mortality for the stable population. There was a benefit from NIV for the post-hospital population based on non-randomized studies, or RCTs from non-Western countries. There was a small but significant reduction in hospital admissions (1–2/year) with NIV across all sub-groups, and a variable reduction in duration of stay with greater reductions in studies from China.

Conclusions: The evidence base on home NIV is considerably larger than previously presented. While NIV may reduce hospital admissions and improve quality of life, there is still little evidence of a reduction in mortality, regardless of country. Individual participant data analysis may clarify which patients would benefit most from NIV.

Citation

Citation: Dretzke J, Wang J, Yao M, et al. Home non-invasive ventilation in COPD: a global systematic review. Chronic Obstr Pulm Dis. 2022; 9(2): 237-251. doi: http://dx.doi.org/10.15326/jcopdf.2021.0242

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Perspective:

A Conceptual Framework for Use of Increased Endurance Time During Constant Work Rate Cycle Ergometry as a Patient-Focused Meaningful Outcome in COPD Clinical Trials

Richard Casaburi, MD, PhD1 Debora D. Merrill, MBA2 Gale Harding, MA3 Nancy Kline Leidy, PhD3 Harry B. Rossiter, PhD1 Ruth Tal-Singer, PhD2 Alan Hamilton, PhD4 on behalf of the CBQC Constant Work Rate Exercise Working Group

Author Affiliations

  1. Rehabilitation Clinical Trials Center, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, United States
  2. COPD Foundation, Washington, DC, United States
  3. Evidera, Bethesda, Maryland, United States
  4. Medical Department, Boehringer Ingelheim, Burlington, Ontario, Canada

Address correspondence to:

Richard Casaburi, PhD, MD
Rehabilitation Clinical Trials Center
The Lundquist Institute at Harbor UCLA Medical Center, CDCRC Building
Torrance, CA 90502
Email: casaburi@ucla.edu
Phone: (424) 201-3000 x7269

Abstract

The Chronic Lung Disease Biomarker and Clinical Outcome Assessment Qualification Consortium (CBQC) evaluates the potential of biomarkers and outcome measures as drug development tools. Exercise endurance is an objective indicator of treatment benefit, closely related to daily physical function. Therefore, it is an ideal candidate for an outcome for drug development trials. Unfortunately, no exercise endurance measure is qualified by regulatory authorities for use in trials of chronic obstructive pulmonary disease (COPD) and no approved COPD therapies have claims of improving exercise endurance. Consequently, it has been challenging for developers to consider this outcome when designing clinical trials for new therapies.

Endurance time during constant work rate cycle ergometry (CWRCE), performed on an electronically braked stationary cycle ergometer, provides an exercise endurance measure under standardized conditions. Baseline individualized work rate for each participant is set using an incremental test. During CWRCE the patient is encouraged to continue exercising for as long as possible. Although not required, physiological and sensory responses (e.g., pulmonary ventilation, heart rate, dyspnea ratings) are frequently collected to support interpretation of endurance time changes. Exercise tolerance limit is reached when the individual is limited by symptoms, unable to maintain pedaling cadence or unable to continue safely. At exercise cessation, exercise duration is recorded.

An CWRCE endurance time increase from the pre-treatment baseline is proposed as a key efficacy endpoint in clinical trials. In COPD, improved exercise endurance has a direct relationship to the experience of physical functioning in daily life, which is a patient-centered, meaningful benefit.

Citation

Citation: Casaburi R, Merrill DD, Harding G, et al. A conceptual framework for use of increased endurance time during constant work rate cycle ergometry as a patient-focused meaningful outcome in COPD clinical trials. Chronic Obstr Pulm Dis. 2022; 9(2): 252-265. doi: http://dx.doi.org/10.15326/jcopdf.2021.0258

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Attitudes Towards Vaccination for Coronavirus Disease 2019 in Patients with Severe Alpha-1 Antitrypsin Deficiency

Oliver J. McElvaney, MD, PhD1,2,3 Brian Cleary, MD2 Daniel D. Fraughen, MD1,2,3 Geraldine Kelly, MBA3 Mark P. Murphy, PhD1 Oisín F. McElvaney, MD, PhD1,2 Peter Branagan, MD1,2 Cedric Gunaratnam, MD1,2 Tomás P. Carroll, PhD1,3 Noel G. McElvaney, MD1,2,3

Author Affiliations

  1. Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
  2. Beaumont Hospital, Dublin, Ireland
  3. Alpha-1 Foundation of Ireland, Dublin, Ireland

Address correspondence to:

Oliver J. McElvaney
Department of Medicine
Royal College of Surgeons in Ireland
Dublin, Ireland
Phone: +353 18093763
Email: olivermcelvaney@rcsi.ie

Abstract

Patients with severe alpha-1 antitrypsin deficiency (AATD) are at increased risk for the development of chronic obstructive pulmonary disease (COPD), particularly if they smoke. This, coupled with their predilection for dysregulated inflammation and autoimmunity, makes affected individuals priority candidates for vaccination against coronavirus disease 2019 (COVID-19). To promote vaccine uptake effectively, an understanding of the factors motivating people to proceed with vaccination is essential. The attitudes of patients with AATD towards COVID-19 vaccination have yet to be described.

We prospectively studied 170 Pi*ZZ genotype AATD patients, 150 patients with nonhereditary (Pi*MM genotype) COPD and 140 Pi*MM genotype individuals without lung disease receiving first-dose vaccination with ChAdOx1 nCoV-19 (AstraZeneca). Patient attitudes towards vaccination and motivations for getting vaccinated were assessed at the time of the vaccine being offered. Following completion of the 2-dose vaccine series, Pi*ZZ patients were then re-assessed regarding their attitudes towards booster vaccination.

The most common primary motivation for accepting vaccination in Pi*ZZ participants ≥50 years old was a fear of illness or death from COVID-19. In contrast, Pi*ZZ patients <50 years most often cited a desire to socialize. The motivation pattern of younger Pi*ZZ AATD patients was similar to that of non-deficient individuals of comparable age, whereas older Pi*ZZ individuals were more closely aligned with Pi*MM COPD and differed from age-matched controls without lung disease. When considering booster vaccination, Pi*ZZ patients were increasingly motivated by a desire to reacquire social freedoms. A desire to reduce the risk of transmission was not a prominent consideration in any of the groups studied. The most commonly cited reason for booster hesitancy was a lack of incentive, given that no additional social freedoms were available to triple-vaccinated individuals compared to those who were double-vaccinated at the time.

Taken together, these data may inform policymakers attempting to promote vaccine uptake among patients with AATD.

Citation

Citation: McElvaney OJ, Cleary B, Fraughen DD, et al. Attitudes towards vaccination for coronavirus disease 2019 in patients with severe alpha-1 antitrypsin deficiency. Chronic Obstr Pulm Dis. 2022; 9(2): 266-273. doi: http://dx.doi.org/10.15326/jcopdf.2022.0288

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Letter to the Editor:

Insights About the Human-Centered Design Analysis as a Tool to Improving Patients’ Tolerance with Non-Invasive Ventilation

Domenica Di Costanzo, MD1 Simon Meredith, DO2 Bushra Mina, MD2 Antonio M. Esquinas, MD, PhD, FCCP, FNIV, FAARC3

Author Affiliations

  1. Department of Respiratory Disease, AORN Sant’Anna e San Sebastiano, Caserta, Italy
  2. Department of Pulmonary and Critical Care, Lenox Hill Hospital, New York, New York, United States
  3. Intensive Care Unit, Hospital Morales Meseguer, Murcia, Spain

Address correspondence to:

Domenica Di Costanzo, MD
Department of Respiratory Disease
AORN Sant’Anna e San Sebastiano
Caserta, Italy
Via Ferdinando Palasciano, 81100 Caserta CE
Telephone: +390823232630
Email: domenica.dicostanzo@libero.it

Abstract

This article does not contain an abstract.

Citation

Citation: Di Costanzo D, Meredith S, Mina B, Esquinas AM. Insights about human-centered design analysis as a tool to improve patients’ tolerance with non-invasive ventilation. Chronic Obstr Pulm Dis. 2022; 9(2): 274-276. doi: http://dx.doi.org/10.15326/jcopdf.2022.0295

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Brief Report:

Adding Granularity of COPD Self-Management to Impact Quality of Life

Maria V. Benzo, MD1 Paul Novotny, MS2 Roberto P. Benzo, MD1

Author Affiliations

  1. Mindful Breathing Laboratory, Division of Pulmonary, Critical Care, and Sleep Medicine, Mayo Clinic, Rochester, Minnesota, United States
  2. Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States

Address correspondence to:

Roberto Benzo, MD, MSc
Email: benzo.roberto@mayo.edu

Abstract

Background: Self-management abilities are a recognized ingredient for living well with chronic obstructive pulmonary disease (COPD), improving all outcomes. Fostering self-management requires a personalized program and patient engagement to make lifestyle decisions.

While some self-management practices are proven effective, like the prompt use of a plan for COPD exacerbations, there is a guideline-recognized gap on specific self-management behaviors that can impact particular COPD symptoms and allow for tailored self-management programs. We aimed to investigate the association of well-defined self-management behaviors with the most common COPD symptoms in a large cohort of patients with COPD.

Methods: We analyzed baseline data of stable COPD patients who participated in 3 National Institutes of Health-funded studies. Symptoms were defined by the 4 domains of the Chronic Respiratory Questionnaire: dyspnea-fatigue-emotions-mastery. The self-management behaviors were the individual items of the Self-Management Ability Scale-30. Lasso regression models were built to explore the association of behaviors with symptoms, adjusting for lung function and age.

Results: We analyzed 512 stable COPD patients, 54% female, age mean (standard deviation [SD]) 69.6 (9.9) years and forced expiratory volume in 1 second percent predicted (FEV1%) 42.2 (19.0).Dyspnea was associated with exercising and self-efficacy for self-care. Emotion was associated with good relationships, self-efficacy for self-care, positivity, and participating in agreeable activities. Fatigue was associated with self-efficacy for self-care, doing exercise, and participating in agreeable activities. Mastery was associated with self-efficacy for self-care, positivity, exercising, and participating in agreeable activities.

Discussion: Our findings provide specific self-management behaviors associated with common COPD symptoms that may inform self-management programs. Positive thinking represents a novel self-management approach to COPD emotions and mastery.

Citation

Citation: Benzo MV, Novotny P, Benzo RP. Adding granularity of COPD self-management to impact quality of life. Chronic Obstr Pulm Dis. 2022; 9(2): 277-284. doi: http://dx.doi.org/10.15326/jcopdf.2021.0277

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Journal Club:

Journal Club: Biologics and Potential for Immune Modulation in Chronic Obstructive Lung Disease

Takudzwa Mkorombindo, MD1 Ron Balkissoon, MD2

Author Affiliations

  1. Lung Health Center, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama, Birmingham, Alabama, United States
  2. Denver, Colorado

Address correspondence to:

Takudzwa Mkorombindo, MD
Email: tmkorombindo@uabmc.edu

Abstract

This article does not contain an abstract.

Citation

Citation: Mkorombindo T, Balkissoon R. Journal club:biologics and potential for immune modulation in chronic obstructive lung disease. Chronic Obstr Pulm Dis. 2022; 9(2): 285-297. doi: http://dx.doi.org/10.15326/jcopdf.2022.0318

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