Chronic Obstructive Pulmonary Diseases:Journal of the COPD Foundation

Articles in Press

Final Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation (JCOPDF) manuscripts are published and available in our Articles in Press section as soon as possible following editorial acceptance. These articles have completed both a rigorous peer review process and a thorough copyediting/editorial acceptance phase. Quarterly, these articles will be compiled into formal issues along with editorials, correspondence and additional themed reviews and features. To receive notifications of the posting of new Articles in Press AND the posting of new JCOPDF issues, sign up for a free subscription here.

Brief History:

A Brief History of Bronchitis in England and Wales

Jonathan H. Widdicombe, DPhil1

Author Affiliations

  1. Department of Physiology and Membrane Biology, University of California – Davis

Address correspondence to:

Jonathan H. Widdicombe, DPhil
Phone: (530)668-9405
E-mail: jhwiddicombe@ucdavis.edu

Abstract

Chronic bronchitis is associated with hypertrophy of airway submucosal glands and with mucus and squamous metaplasia of the surface epithelium. A historical review of research on these and other pathological changes is provided. Next, from annual reports of the Registrar-General’s Office (and later the Office of National Statistics), death rates per unit population from acute and chronic bronchitis (a term that here includes chronic obstructive pulmonary disease [COPD]) are calculated for England and Wales from 1838 to the present. It is argued that a large increase in the death rate between 1838 and 1879, from all forms of bronchitis combined, was due primarily to increased levels of atmospheric coal smoke, whereas a decrease from 1879 to 1935 was due to progressively cleaner air. Between 1935 and the mid-1960s, mortality from chronic bronchitis among men increased dramatically, after which it has fallen, a pattern that parallels changes in cigarette smoking. Finally, a brief historical review of the treatments for chronic bronchitis is presented.

Citation

Citation: Widdicombe JH. A brief history of bronchitis in England and Wales. Chronic Obstr Pulm Dis. 2020; 7(4):In press. doi: http://dx.doi.org/10.15326/jcopdf.7.4.2020.0135

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Original Research:

Design of the Redefining Therapy in Early COPD Study

MeiLan K. Han, MD, MS1 Wen Ye, PhD2 Dong-Yun Kim, PhD3 Prescott Woodruff, MD, MS4 for the Pulmonary Trials Cooperative Investigators

Author Affiliations

  1. Division of Pulmonary and Critical Care, University of Michigan, Ann Arbor
  2. School of Public Health, University of Michigan, Ann Arbor
  3. National Institutes of Health, Bethesda, Maryland
  4. Division of Pulmonary and Critical Care, University of California, San Francisco

Address correspondence to:

MeiLan K. Han, MD, MS
Phone: (734) 936-5201
Email: mrking@umich.edu

Abstract

Redefining Therapy in Early COPD (RETHINC) is a 12-week multicenter, randomized, double-blind, placebo-controlled, parallel-group study to assess the efficacy and safety of indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily in symptomatic current and former smokers with respiratory symptoms as defined by COPD Assessment Test (CAT) score ≥ 10 despite preserved spirometry defined by post-bronchodilator forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio ≥ 0.70. Recruitment began in July 2017 with the goal of enrolling 580 participants. The baseline examination includes spirometry (with slow and forced maneuvers) and symptom questionnaires. A follow-up phone call at 4 weeks assesses symptoms and safety. The second and final visit at week 12 includes spirometry before and after study drug (hourly over 3 hours) and follow-up symptom questionnaires. The primary endpoint is the proportion of individuals who experience a 4-unit improvement in St George’s Respiratory Questionnaire (SGRQ) score at 12 weeks without treatment failure, defined as an increase in lower respiratory symptoms necessitating treatment with active, long-acting inhaled bronchodilators, corticosteroids or antibiotics. Key secondary endpoints include the proportion of individuals with a 2-unit improvement in the CAT score; 1-unit improvement in the Baseline Dyspnea Index (BDI) and Transition Dyspnea Index (TDI), both a 4-unit improvement in SGRQ and a 1-unit improvement in BDI/TDI; and mean change in SGRQ, CAT and BDI/TDI. Other secondary endpoints include area under the curve 0-3 hours for FEV1 after study drug, change from baseline in trough inspiratory capacity, forced expiratory flow 25%-75% of FVC (FEF25-75) iso-volume FEF25-75 and mean change in symptoms and rescue medication use based on daily diary. We anticipate results to be available in 2021. This paper describes the RETHINC study and explains the rationale behind it.

Citation

Citation: Han MK, Ye W, Kim DY, Woodruff P; Pulmonary Trials Cooperative investigators. Design of the redefining therapy in early COPD study. Chronic Obstr Pulm Dis. 2020; 7(4):In press. doi: http://dx.doi.org/10.15326/jcopdf.7.4.2020.0157

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Home-Based Palliative Care: Perspectives of Chronic Obstructive Pulmonary Disease Patients and Their Caregivers

Karen F. Hyden, PhD, MSN/Ed, RN1 Heather L. Coats, PhD, MSN, RN1 Paula M. Meek, PhD, RN2

Author Affiliations

  1. College of Nursing, University of Colorado Anschutz Medical Campus, Aurora
  2. College of Nursing, University of Utah, Salt Lake City

Address correspondence to:

Karen F. Hyden, PhD, MSN/Ed
Phone: (615)473-9645
Email: Karen.2.Hyden@CUAnschutz.edu

Abstract

Background: Home-based palliative care (HBPC) is an important aspect of care for patients with moderate to advanced stages of chronic obstructive pulmonary disease (COPD) and their caregivers. HBPC provides symptom management, advanced care planning and goals of care conversations in the home, with the goal of maximizing quality of life and minimizing health care utilization. There is a gap in the knowledge of how the patients with COPD and their caregivers experience HBPC. The overall purpose of this study is to describe which aspects of HBPC were the most meaningful to patients with COPD, and their caregivers.

Methods: Through a descriptive design with narrative analysis methodology, we interviewed COPD patients and their caregivers to investigate their experience of HBPC received in the 30 days post hospitalization for a COPD exacerbation. A thematic analysis was conducted and the patient and caregiver interviews were analyzed in dyad using thematic analysis.

Results: A total of 10 dyads were interviewed. Patients and their caregivers perceived 3 times as many facilitators as barriers of receiving home-based palliative care in the 30 days post hospitalization for a COPD exacerbation. The outcomes of this study provide information that describes the aspects of HBPC that patients and their caregivers found most meaningful.

Conclusion: An understanding of the most meaningful aspects of HBPC from the perspectives of the patients with COPD and their caregivers can be used to inform the development of the best model for HBPC for this patient population.

Citation

Citation: Hyden KF, Coats HL, Meek PM. Home-based palliative care: perspectives of chronic obstructive pulmonary disease patients and their caregivers. Chronic Obstr Pulm Dis. 2020; 7(4):In press. doi: http://dx.doi.org/10.15326/jcopdf.7.4.2020.0144

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Tolerability and Safety of High-Flow Nasal Therapy in Patients Hospitalized with an Exacerbation of COPD

Aloknath A. Pandya, MD1* Lii-Yoong Helga Criner, RN, CCRN1 JiJi Thomas, MBBS1 Michael Jacobs, PharmD1 Gerard J. Criner, MD1

Author Affiliations

  1. Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania

*Dr. Pandya is now with Pulmonary Associates of Drexel Hill, Drexel Hill, Pennsylvania

Address correspondence to:

Aloknath Pandya, MD
Phone:(267) 858-2669
Email: apandya1@gmail.com

Abstract

Background: The effect of high-flow nasal therapy (HFNT) in individuals with an exacerbation of chronic obstructive pulmonary disease (COPD) and hypercapnia is not well studied. We assessed patient tolerance and impact of air-gas therapy delivered by humidified HFNT (20-35 L/min) on gas exchange in hypercapnic COPD patients during hospitalization for COPD exacerbation. We hypothesized that HFNT use would be safe and well tolerated in individuals hospitalized for COPD exacerbation regardless of the degree of hypercapnia.

Methods: Patients hospitalized for a COPD exacerbation were included if they were hypercapnic (arterial partial pressure of carbon dioxide [PaCO2] > 45 mmHg), ≥ 10 pack-year history, and agreed to treatment with HFNT, along with daily arterial blood gas (ABG) samples and bedside spirometry. They were placed on a HFNT system following admission for at least 3 days with an air-gas blend to maintain a flow rate between 20-35 L/min and fraction of inspired oxygen (FiO2) titrated to keep oxygen saturation (SaO2) values > 90%. Patient tolerance of HFNT and evidence of clinical deterioration as defined by worsening hypoxia or hypercapnia was the primary endpoint.

Results: Ten consecutive patients participated in the study. The patients had frequent prior exacerbations, were hypercapnic, dyspneic, and gas trapped. Participants received an air-gas flow rate (median [interquartile range (IQR)] 25 (IQR 20-30) L/min and FiO2 of 30 (IQR 30-30) %. There was no increase in PaCO2­ levels (p = 0.26) or dyspnea (Borg scale, p= 0.52) while using HFNT. No patient discontinued HFNT, had further decompensation, required non-invasive ventilation or intubation during the study period.

Conclusion: In a pilot study, patients experiencing a severe COPD exacerbation were able to tolerate continuous HFNT safely regardless of degree of hypercapnia.

Citation

Citation: Pandya AA, Criner LH, Thomas J, Jacobs M, Criner GJ. Tolerability and safety of high-flow nasal therapy in patients hospitalized with an exacerbation of COPD. Chronic Obstr Pulm Dis. 2020; 7(4):In press. doi: http://dx.doi.org/10.15326/jcopdf.7.4.2020.0137

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Hypercapnia in Advanced Chronic Obstructive Pulmonary Disease: A Secondary Analysis of the National Emphysema Treatment Trial

Anne M. Mathews, MD1 Nicholas G. Wysham, MD2 Jichun Xie, PhD1 Xiaodi Qin, PhD1 Coral X. Giovacchini, MD1 Magnus Ekström, MD3 Neil R. MacIntyre, MD1

Author Affiliations

  1. Duke University Medical Center, Durham North Carolina
  2. Department of Pulmonary and Critical Care, the Vancouver Clinic and School of Medicine, Washington State University, Vancouver
  3. Department of Clinical Sciences, Division of Respiratory Medicine and Allergology, Lund University, Lund, Sweden

Address correspondence to:

Neil MacIntyre, MD
Box 3911, Room 1120
Duke University Medical Center
Erwin Road
Durham, NC 27710
Email: neil.macintyre@duke.edu

Abstract

Rationale: Hypercapnia develops in one third of patients with advanced chronic obstructive pulmonary disease (COPD) and is associated with increased morbidity and mortality. Multiple factors in COPD are thought to contribute to the development of hypercapnia including increased carbon dioxide (CO2) production, increased dead space ventilation, and the complex interactions of deranged respiratory system mechanics, inspiratory muscle overload and the ventilatory control center in the brainstem. However, these factors have not previously been systematically analyzed in a large, well-characterized population of severe COPD patients.

Methods: This is a secondary analysis of the clinical, physiologic and imaging data from the National Emphysema Treatment Trial (NETT). All patients with complete baseline data for the key predictor variables were included. An inclusive list of 32 potential predictor variables were selected a priori based on consensus of the investigators and literature review. Stepwise variable selection yielded 10 statistically significant associations in multivariate regression.

Results: A total of 1419 patients with severe COPD were included in the analysis; mean age 66.4 years (standard deviation 6.3), 38% females, and 422 (29.7%) had baseline hypercapnia. Key variables associated with hypercapnia were low resting partial pressure of oxygen in blood, low minute ventilation (Ve), high volume of exhaled carbon dioxide, low forced expiratory volume in 1 second, high residual volume, lower % emphysema on chest computed tomography, use of oxygen, low ventilatory reserve (high Ve/maximal voluntary ventilation), and not being at high altitude. Low diffusing capacity for carbon monoxide showed a positive association with hypercapnia in univariate analysis but a negative correlation in multivariate analysis. Measures of dyspnea and quality of life did not associate with degree of hypercapnia in multivariable analysis.

Conclusions: Hypercapnia in a well-characterized cohort with severe COPD and emphysema is chiefly related to poor lung mechanics, high CO2 production, and a reduced ventilatory capability. Hypercapnia is less impacted by gas exchange abnormalities or the presence of emphysema.

Citation

Citation: Matthews AM, Wysham NG, Xie J, et al. Hypercapnia in advanced chronic obstructive pulmonary disease: a secondary analysis of the National Emphysema Treatment Trial. Chronic Obstr Pulm Dis. 2020; 7(4):In press. doi: http://dx.doi.org/10.15326/jcopdf.7.4.2020.0176

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A Risk Prediction Model for Mortality Among Smokers in the COPDGene® Study

Matthew Strand, PhD1 Erin Austin, PhD2 Matthew Moll, MD3 Katherine A. Pratte, MSPH, PhD1 Elizabeth A. Regan, MD, PhD1 Lystra P. Hayden, MD, MMSc3 Surya P. Bhatt, MD4 Aladin M. Boriek, PhD5 Richard Casaburi, PhD, MD6 Edwin K. Silverman, MD, PhD3 Spyridon Fortis, MD7 Ingo Ruczinski, PhD8 Harald Koegler, MD9 Harry B. Rossiter, PhD6 10 Mariaelena Occhipinti, MD, PhD11* Nicola A. Hanania, MD, MS5 Hirut T. Gebrekristos, PhD12 David A. Lynch, MB1 Ken M. Kunisaki, MD13 Kendra A. Young, MSPH, PhD14 Jessica C. Sieren, PhD7 Margaret Ragland, MD, MS14 John E. Hokanson, MPH, PhD14 Sharon M. Lutz, PhD15 Barry J. Make, MD1 Gregory L. Kinney, MPH, PhD14 Michael H. Cho, MD, MPH3 Massimo Pistolesi, MD11 Dawn L. DeMeo, MD, MPH3 15 Frank C. Sciurba, MD16 Alejandro P. Comellas, MD7 Alejandro A. Diaz, MD3 Igor Barjaktarevic, MD, PhD17 Russell P. Bowler, MD, PhD1 Richard E. Kanner, MD18 Stephen P. Peters, MD, PhD19 Victor E. Ortega, MD, PhD19 Mark T. Dransfield, MD4 James D. Crapo, MD1

Author Affiliations

  1. National Jewish Health, Denver, Colorado
  2. University of Colorado at Denver
  3. Brigham and Women’s Hospital, Boston, Massachusetts
  4. University of Alabama at Birmingham
  5. Baylor College of Medicine, Houston, Texas
  6. The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California
  7. University of Iowa, Iowa City
  8. Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
  9. Boehringer-Ingelheim, Ingelheim, Germany
  10. University of Leeds, Leeds, United Kingdom
  11. University of Florence, Florence, Italy
  12. Morehouse School of Medicine, Atlanta, Georgia
  13. Minneapolis Veterans Administration Health Care System, Minnesota
  14. University of Colorado Anschutz Medical Campus, Aurora
  15. Harvard Medical School, Harvard University, Boston, Massachusetts
  16. University of Pittsburgh, Pittsburgh, Pennsylvania
  17. David Geffen School of Medicine, University of California-Los Angeles, Los Angeles
  18. School of Medicine, University of Utah, Salt Lake City
  19. Wake Forest School of Medicine, Wake Forest University, Winston-Salem, North Carolina

* Dr. Occhipinti is now at the Imaging Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland

Address correspondence to:

Matthew Strand, PhD
Phone: (303) 398-1862
Email: strandm@njhealth.org

Abstract

Background: Risk factor identification is a proven strategy in advancing treatments and preventive therapy for many chronic conditions. Quantifying the impact of those risk factors on health outcomes can consolidate and focus efforts on individuals with specific high-risk profiles. Using multiple risk factors and longitudinal outcomes in 2 independent cohorts, we developed and validated a risk score model to predict mortality in current and former cigarette smokers.

Methods: We obtained extensive data on current and former smokers from the COPD Genetic Epidemiology (COPDGene®) study at enrollment. Based on physician input and model goodness-of-fit measures, a subset of variables was selected to fit final Weibull survival models separately for men and women. Coefficients and predictors were translated into a point system, allowing for easy computation of mortality risk scores and probabilities. We then used the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) cohort for external validation of our model.

Results: Of 9867 COPDGene participants with standard baseline data, 17.6% died over 10 years of follow-up, and 9074 of these participants had the full set of baseline predictors (standard plus 6-minute walk distance and computed tomography variables) available for full model fits. The average age of participants in the cohort was 60 for both men and women, and the average predicted 10-year mortality risk was 18% for women and 25% for men. Model time-integrated area under the receiver operating characteristic curve statistics demonstrated good predictive model accuracy (0.797 average), validated in the external cohort (0.756 average). Risk of mortality was impacted most by 6-minute walk distance, forced expiratory volume in 1 second and age, for both men and women.

Conclusions: Current and former smokers exhibited a wide range of mortality risk over a 10- year period. Our models can identify higher risk individuals who can be targeted for interventions to reduce risk of mortality, for participants with or without chronic obstructive pulmonary disease (COPD) using current Global initiative for chronic Obstructive Lung Disease (GOLD) criteria.

Citation

Citation: Strand M, Austin E, Moll M, et al. A risk prediction model for mortality among smokers in the COPCGene® study. Chronic Obstr Pulm Dis. 2020; 7(4):In press. doi: http://dx.doi.org/10.15326/jcopdf.7.4.2020.0146

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The Effect of Metabolic Syndrome Status on Lung Function and Patient-reported Outcomes in Patients with COPD Receiving Nebulized Glycopyrrolate

Brian Carlin, MD1 Gary T. Ferguson, MD2 Ayca Ozol-Godfrey, PhD3 Thomas Goodin, PhD3 Shahin Sanjar, PhD3

Author Affiliations

  1. Sleep Medicine and Lung Health Consultants, LLC, Pittsburgh, Pennsylvania
  2. Pulmonary Research Institute of Southeast Michigan, Farmington Hills, Michigan
  3. Sunovion Pharmaceuticals, Inc., Marlborough, Massachusetts

Address correspondence to:

Brian Carlin, MD
Sleep Medicine and Lung Health Consultants
P.O. Box 174
Ingomar, PA 15127 USA
Phone: +1 (412) 351-6545
E-mail: bwcmd@yahoo.com

Abstract

Background: Concurrent chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MetS) represent an important clinical phenotype with overlapping symptomology. The effect of MetS in COPD patients was assessed following treatment with nebulized glycopyrrolate (GLY; administered via eFlow® Closed System Nebulizer).

Methods: Posthoc analyses were performed on pooled lung function, patient-reported outcome (PRO) and safety data by MetS status from patients treated with placebo, GLY 25 and 50 mcg twice daily in two 12-week studies (GOLDEN 3 and 4; N=1293). Patients with MetS were characterized as having ≥ 3 of hypertension, hyperlipidemia, diabetes, body mass index (BMI) > 30 kg/m2 risk factors. The results are presented for the Food and Drug Administration-approved GLY 25 mcg dose.

Results: A total of25% of patients met MetS criteria.At baseline, the MetS subgroup had higher BMIs, more ex-smokers, greater incidences of cardiovascular risk factors, and MetS-specific risk factors were 2–14 times higher than non-MetS. At 12 weeks, GLY produced significant, clinically important improvements (MetS: 0.121 L; non-MetS: 0.083 L) in trough forced expiratory volume in 1 second. In the non-MetS group, significant improvements occurred in the St George’s Respiratory Questionnaire (MetS: –2.28, p=0.157; non-MetS: –3.71) and Evaluating Respiratory Symptoms in COPD tool (MetS: 0.42, p=0.574; non-MetS: –1.61) total scores. Incidence of adverse events was similar with GLY versus placebo regardless of MetS status.

Conclusions: GLY was well-tolerated and significantly improved lung function regardless of MetS status, while significant PRO improvements occurred in non-MetS patients. These results highlight the importance of comorbidities on bronchodilator responses and patient symptoms in COPD patients.

Citation

Citation: Carlin B, Ferguson GT, Ozol-Godfrey A, Goodin T, Sanjar S. The effect of metabolic syndrome status on lung function and patient-reported outcomes in patients with COPD receiving nebulized glycopyrrolate. Chronic Obstr Pulm Dis. 2020; 7(4):In press. doi: http://dx.doi.org/10.15326/jcopdf.7.4.2020.0145

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