Author Affiliations

1. COPD Foundation, Washington, DC, United States
2. Columbia University Medical Center, New York, New York, United States

Address correspondence to:

Danielle Boyce, MPH
COPD Foundation
Email: dboyce@copdfoundation.org
Phone: 267-273-8327

Abstract

Objectives: To investigate telemedicine adoption, emergency department avoidance, and related characteristics of patients with chronic obstructive pulmonary disease (COPD) with and without exacerbations since the coronavirus 2019 (COVID-19) pandemic began.

Methods: We conducted the second of a series of online surveys via SurveyMonkey.com of people with COPD between May 1, 2020 and May 31, 2020. Frequency, percentage, and Fisher’s exact test (2-sided) were calculated using SPSS version 26.

Results: More than half of respondents (157, 64%), indicated that they started using telemedicine in 2020. A total of 47% of respondents reported having had at least 1 exacerbation since January 1, 2020. Respondents who had at least 1 exacerbation in 2020 were more likely to start using telemedicine in 2020 than respondents who did not report any exacerbation in 2020 (75.7% versus 54.3%, p < 0.001). Respondents reporting a 2020 exacerbation indicated having a significantly higher avoidance of emergency health care since the pandemic began (27.8%) as compared to those who did not have an exacerbation in 2020 (10.1%), p < 0.001.

Conclusions: In response to social distancing and other COVID-19 precautions, people with COPD are avoiding traditional, in-person health care environments and turning to telemedicine to prevent and manage exacerbations. Further investigation is needed to identify best practices in and barriers to telemedicine in this population.

Citation

Citation: Boyce DM, Thomashow BM, Sullivan J, Tal-Singer R. New adopters of telemedicine during the coronavirus-19 pandemic in respondents to an online community survey: the case for access to remote management tools for individuals with chronic obstructive pulmonary disease. J COPD F. 2021; 8(2): 213-218. doi: http://doi.org/10.15326/jcopdf.8.2.2020.0181

Keywords

COPD, exacerbations, COVID-19, telemedicine, telehealth

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Author Affiliations

1. Imaging Department, University Medical Center Utrecht, Utrecht, the Netherlands
2. Division of Biostatistics, Environment and Health, National Jewish Health, Denver, Colorado, United States
3. Department of Radiology, University Medical Center Utrecht, Utrecht, the Netherlands
4. Diagnostic Image Analysis Group, Radboud University Medical Center, Nijmegen, the Netherlands
5. Division of Pulmonary and Critical Care, University of Michigan Health System, Ann Arbor, Michigan, United States
6. Department of Radiology, National Jewish Health, Denver, Colorado, United States
7. Imbio LLC, Minneapolis, Minnesota, United States
8. Department of Radiology, University of Michigan, Ann Arbor, Michigan, United States
9. Center for Molecular Imaging, University of Michigan, Ann Arbor, Michigan, United States
10. Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, United States
11. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, United States
12. Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, National Jewish Health, Denver, Colorado, United States
13. Division of Rheumatology, Department of Medicine, National Jewish Health, Denver, Colorado, United States

Address correspondence to:

Esther Pompe, MD
Imaging Department
University Medical Center
UtrechtPostbus 85500
3508 GA Utrecht
Postbox: E.03.511
E-mail: e.pompe@umcutrecht.nl
Phone: +31 88 75 50846

Abstract

Background: Little is known about factors associated with emphysema progression in cigarette smokers. We evaluated factors associated with change in emphysema and forced expiratory volume in 1 second (FEV₁) in participants with and without chronic obstructive pulmonary disease (COPD).

Methods: This retrospective study included individuals participating in the COPD Genetic Epidemiology study who completed the 5-year follow-up, including inspiratory and expiratory computed tomography (CT) and spirometry. All paired CT scans were analyzed using micro-mapping, which classifies individual voxels as emphysema or functional small airway disease (fSAD). Presence and progression of emphysema and FEV₁ were determined based on comparison to nonsmoker values. Logistic regression analyses were used to identify clinical parameters associated with disease progression.

Results: A total of 3088 participants were included with a mean ± SD age of 60.7±8.9 years, including 72 nonsmokers. In all Global initiative for chronic Obstructive Lung Disease (GOLD) stages, the presence of emphysema at baseline was associated with emphysema progression (odds ratio [OR]: GOLD 0: 4.32; preserved ratio-impaired spirometry [PRISm]; 5.73; GOLD 1: 5.16; GOLD 2: 5.69; GOLD 3/4: 5.55; all p ≤0.01). If there was no emphysema at baseline, the amount of fSAD at baseline was associated with emphysema progression (OR for 1% increase: GOLD 0: 1.06; PRISm: 1.20; GOLD 1: 1.7; GOLD 3/4: 1.08; all p ≤ 0.03).In 1735 participants without spirometric COPD, progression in emphysema occurred in 105 (6.1%) participants and only 21 (1.2%) had progression in both emphysema and FEV₁.

Conclusions: The presence of emphysema is an important predictor of emphysema progression. In patients without emphysema, fSAD is associated with the development of emphysema. In participants without spirometric COPD, emphysema progression occurred independently of FEV₁ decline.

Citation

Citation: Pompe E, Moore CM, Mohamed Hoesein FAA, et al for the COPDGene Investigators. Progression of emphysema and small airways disease in cigarette smokers. J COPD F. 2021; 8(2): 198-212. doi: http://doi.org/10.15326/jcopdf.8.2.2020.0140

Keywords

COPD, computed tomography, emphysema, air trapping, functional small airways disease

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Author Affiliations

1. Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, United States
2. Department of Pulmonary Medicine, Cleveland Clinic Florida, Weston, Florida, United States

Address correspondence to:

Samuel Gurevich, MD
Respiratory Center
Cleveland Clinic Florida Weston
Building A2950 Cleveland Clinic Blvd
Weston, FL 33331
Ph: (954) 659-5450
Fax: (954) 659-5451
Email: Gurevis@ccf.org

Abstract

Alpha-1 antitrypsin deficiency (AATD) is a common but highly underdiagnosed genetic disorder that may lead to chronic obstructive pulmonary disease (COPD), bronchiectasis, and liver disease. Early diagnosis is key to altering the course of disease as well as informing family members of potential risk. This randomized, prospective observational study compares the different testing modalities for AATD testing of at-risk patients initiated in the pulmonary function testing (PFT) laboratory. Providing a recommendation with a prescription for serologic testing, providing a finger-stick testing method (AlphaKit), and providing a buccal swab testing method (AlphaID) were compared to the community standard of referring the patient back to the PFT-ordering provider only. Results show that testing directly in the PFT laboratory has an odds ratio (OR) for completing testing of 35.14 (5.33 - 999.99), p-value of <0.0001, for buccal swab testing and an OR of 17.09 (2.58 - 729.99), p-value of 0.0002, for finger-stick testing compared to the community standard. Providing a prescription was no better than referral back to the PFT-ordering provider with an OR of 2.61(0.33 - 119.36), p-value of 0.6412. Resources needed to have testing performed by the Respiratory Therapy department were minimal with an average time of 1 to 5 minutes per patient tested. Causes of testing refusal were also identified. In conclusion, direct testing for AATD by respiratory therapists at the conclusion of PFT testing shows a significant improvement in rates of testing, especially with testing that utilizes buccal swab sample collection.

Citation

Citation: Gurevich S, Daya A, Da Silva C, Girard C, Rahaghi F. Improving screening for alpha-1 antitrypsin with direct testing in the pulmonary function testing laboratory. J COPD F. 2021; 8(2): 190-197. doi: http://doi.org/10.15326/jcopdf.8.2.2020.0179

Keywords

COPD, chronic obstructive pulmonary disease, alpha-1 antitrypsin deficiency, AlphaKit, AlphaID

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Author Affiliations

1. Mindful Breathing Lab, Mayo Clinic, Rochester Minnesota, United States

Address correspondence to:

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

Abstract

This article does not contain an abstract.

Citation

Citation: Benzo M, Benzo R. Thealchemy for a behavior change in COPD: the combination of personalized care, the proper environment, patient motivation, and the right tools. J COPD F. 2021; 8(1): 1-3. doi: http://doi.org/10.15326/jcopdf.8.1.2020.0197

Keywords

alpha-1 antitrypsin, behavior change, patient motivation, exercise program, weight management

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Click to read The Alchemy for a Behavior Change in COPD: The Combination of Personalized Care, the Proper Environment, Patient Motivation, and the Right Tools

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Author Affiliations

1. Denver, Colorado, United States

Address correspondence to:

Ron Balkissoon, MD, MSc, DIH, FRCPC
balkissoonr@njhealth.org

Abstract

This article does not contain an abstract.

Citation

Citation: Balkissoon R.Journal club—Do inhaled corticosteroids reduce all-cause mortality in chronic obstructive pulmonary disease? What is the latest evidence? J COPD F. 2021; 8(1): 177-184. doi: http://doi.org/10.15326/jcopdf.8.1.2020.0196

Keywords

COPD, inhaled corticosteroids, chronic obstructive pulmonary diseases, all-cause mortality

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Click to read Journal Club: Do Inhaled Corticosteroids Reduce All-Cause Mortality in Chronic Obstructive Pulmonary Disease? What is the Latest Evidence?

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Author Affiliations

1. College of Nursing, Medical University of South Carolina, Charleston, South Carolina, United States

Address correspondence to:

Jenna Tobin, MSN, RN, FNP-C
Phone: 610-761-7768
Email: jlee213@msn.com

Abstract

This article does not contain an online supplement.

Citation

Citation: Bradley C, Martin R, Porter C, Richardson K, Stress A, Tobin JL. Palliative care referral in the chronic obstructive pulmonary disease population. J COPD F. 2021; 8(1): 4-6. doi: http://doi.org/10.15326/jcopdf.8.1.2020.0195

Keywords

COPD, palliative care, palliative care referral, timing for palliative care referral

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Click to read Palliative Care Referral in the Chronic Obstructive Pulmonary Disease Population

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Author Affiliations

1. Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
2. University Hospitals Birmingham, United Kingdom

Address correspondence to:

Alice M. Turner
Email: a.m.turner@bham.ac.uk
Phone: +44 (0) (121) 371-3885

Abstract

Alpha-1 antitrypsin deficiency (AATD) is an important risk factor for development of chronic obstructive pulmonary disease (COPD). Patients with AATD classically develop a different pattern of lung disease from those with usual COPD, decline faster and exhibit a range of differences in pathogenesis, all of which may be relevant to phenotype and/or impact of exacerbations. There are a number of definitions of exacerbation, with the main features being worsening of symptoms over at least 2 days, which may be associated with a change in treatment. In this article we review the literature surrounding exacerbations in AATD, focusing, in particular, on ways in which they may differ from such events in usual COPD, and the potential impact on clinical management.

Citation

Citation: Smith DJ, Ellis PR, Turner AM. Exacerbations of lung disease in alpha-1 antitrypsin deficiency. J COPD F. 2021; 8(1): 162-176. doi: http://doi.org/10.15326/jcopdf.8.1.2020.0173

Keywords

COPD, emphysema, chronic obstructive pulmonary disease, alpha-1 antitrypsin deficiency, exacerbation, neutrophil

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Author Affiliations

1. Pulmonary Division, Department of Medicine, Lakewood Regional Medical Center, Lakewood, California, United States and David Geffen School of Medicine at University of California-Los Angeles Health Sciences, Los Angeles, California, United States
2. Department of Pathology, Lakewood Regional Medical Center, Lakewood, California, United States
3. Department of Pathology, Katholieke Univeritair Ziekenhuis Gasthuisberg, Leuven, Belgium
4. University of British Columbia James Hogg Research Centre, St. Paul`s Hospital Vancouver, British Columbia, Canada
5. Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at University of California-Los Angeles Health Sciences, Los Angeles, California, United States
6. Independent pulmonary function investigator, Lakewood, California, United States
7. Department of Radiology, Lakewood Regional Medical Center, Lakewood, California, United States
8. Department of Clinical and Experimental Medicine, Katholieke Univeritair Leuven-University of Leuven and University Hospitals Leuven, Leuven, Belgium
9. Affiliated Pathologists Medical Group, Rancho Dominguez, California, United States
10. Cardiovascular Research Institute and Departments of Medicine, Physiology, and Radiology, School of Medicine, University of California San Francisco, San Francisco, California, United States

Address correspondence to:

Arthur F. Gelb MD
3650 E. South St., Suite 308
Lakewood, Calif. 90712
Phone: (562)565-5333
Email: afgelb@msn.com

Abstract

Background: Recent studies have emphasized the difficulty of early detection of chronic obstructive pulmonary disease (COPD) in symptomatic smokers with normal routine spirometry. This includes post-bronchodilator normal forced expiratory volume in 1 second (FEV₁)(L)≥80% predicted, forced vital capacity (FVC)(L)≥80% predicted, and FEV₁/FVC ≥70% or greater than age corrected lower limit of normal (LLN). However, in COPD the pathologic site of small airway obstruction and emphysema begins in the small peripheral airways ≤2 mm id which normally contribute <20% of total airway resistance.

Methods: Expiratory airflow at high and low lung volumes post-bronchodilator were measured and correlated with lung computed tomography (CT) and lung pathology (6 patients) in 16 symptomatic, treated smokers, and all with normal routine spirometry.

Results: Despite normal routine spirometry, all16 patients had isolated, abnormal forced expiratory flow at 75% of FVC (FEF₇₅) using data from Knudson et al, Hankinson et al NHAMES III, and Quanjer et al and the Global Lung Function Initiative. This reflects isolated detection of small airways obstruction and/or emphysema. Measuring airflow at FEF₅₀ detected only 8 of 16 patients, maximal expiratory flow at 25%-75% of FVC (MEF_25-75) only 4 of 16, residual volume (RV) 4 of 16, and RV to total lung capacity ratio only 2 of 16. There was excellent correlation between limited lung pathology and lung CT for absence of emphysema.

Conclusions: This study confirms our earlier observations that detection of small airways obstruction and/or emphysema, in symptomatic smokers with normal routine spirometry, requires analysis of expiratory airflow at low lung volumes, including FEF₇₅. Dependence upon normal routine spirometry may result in clinical and physiologic delay in the diagnosis and treatment in symptomatic smokers with emphysema and small airways obstruction.

Citation

Citation: Gelb AF, Yamamoto A, Verbeken EK, et al. Normal routine spirometry can mask COPD and emphysema in symptomatic smokers. J COPD F. 2021; 8(1): 124-134. doi: http://doi.org/10.15326/jcopdf.8.1.2020.0176

Keywords

COPD, emphysema, chronic obstructive pulmonary disease, spirometry, small airways obstruction, forced expiratory flow at 75% of FVC, FEF₇₅

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Click to read Normal Routine Spirometry Can Mask COPD/Emphysema in Symptomatic Smokers

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Author Affiliations

1. Cone Health, Greensboro, North Carolina, United States
2. Area Health Education Center, Greensboro, North Carolina, United States
3. Eshelman School of Pharmacy, Chapel Hill, University of North Carolina, North Carolina, United States
4. Nebraska Medicine, Omaha, Nebraska, United States

Address correspondence to:

Jennifer Kim, PharmD
Email: jen.kim@conehealth.com
Phone: (336)832-7885

Abstract

Background: Mortality risk from chronic obstructive pulmonary disease (COPD) increases significantly in the first year after a 30-day hospital readmission.

Objective: To evaluate a comprehensive and collaborative pharmacist transitions of care service for patients hospitalized with COPD compared to usual care.

Methods: In this within-site, retrospective study, discharge counseling, medication reconciliation, medication access assistance, therapy changes, and post-discharge long-term follow-up were provided to underserved adult patients with a primary care provider at the study clinic and admitted to the affiliated hospital with a primary diagnosis of COPD exacerbation. Primary outcome was a 180-day composite of COPD-related hospitalizations and emergency department (ED) visits. Secondary outcomes were 30-, 60-, 90-, and 180-day events, costs, pharmacist interventions, time to follow-up, and pneumonia.

Results: Sixty-five patients were identified with a total of 101 index admissions. The mean age was 62.5 years, approximately 55.3% were female, and 67.7% were black or African American. The primary composite was significantly lower in the pharmacist intervention group compared to usual care (mean difference 0.82, P=0.0364, 95% confidence interval [CI] 0.05–1.60), driven by lower 30-day hospitalizations in the intervention group (mean difference 0.15, P=0.0099, 95% CI 0.04–0.27). Cost associated with COPD-related hospitalizations was significantly lower in the pharmacist intervention group compared to usual care ($173,808, P = 0.0330) as well as before intervention ($79,662, P=0.0233). There was no significant difference in time to follow-up or pneumonia.

Conclusions: A comprehensive, collaborative pharmacist transitions of care service significantly reduced 30-day COPD-related hospital readmissions, ED re-visits, and associated costs in an underserved population.

Citation

Citation: Kim J, Lin A, Absher R, Makhlouf T, Wells C. Comprehensive and collaborative pharmacist transitions of care service for underserved patients with chronic obstructive pulmonary disease. J COPD F. 2021; 8(1): 152-161. doi: http://doi.org/10.15326/jcopdf.8.1.2019.0175

Keywords

chronic obstructive pulmonary disease, care transitions, implementation science, quasi-experimental study design, interdisciplinary

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Author Affiliations

1. Division of Pulmonary Sciences and Critical Care Medicine, Colorado Pulmonary Outcomes Research Group, Aurora, Colorado, United States
2. Division of Health Care Policy and Research, Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, United States
3. Institute for Health Research, Kaiser Permanente Colorado, Denver, Colorado, United States
4. National Jewish Health, Denver, Colorado, United States
5. Denver Veterans Administration Medical Center, Denver, Colorado, United States
6. Department of Family Medicine, High Plains Research Network, University of Colorado Denver, Anschutz Medical Campus, United States

*Authors contributed equally to the study

Address correspondence to:

R. William Vandivier, MD
Professor of Medicine
Department of Medicine
Division of Pulmonary Sciences and Critical Care Medicine
University of Colorado-Denver
Aurora, CO 80045
Phone: (303)724-6068
Email: Bill.Vandivier@cuanschutz.edu

Abstract

Background: Up to 50% of chronic obstructive pulmonary disease (COPD) patients do not receive recommended care for COPD. To address this issue, we developed Proactive Integrated Care (Proactive iCare), a health care delivery model that couples integrated care with remote monitoring.

Methods: We conducted a prospective, quasi-randomized clinical trial in 511 patients with advanced COPD or a recent COPD exacerbation, to test whether Proactive iCare impacts patient-centered outcomes and health care utilization. Patients were allocated to Proactive iCare (n=352) or Usual Care ( =159) and were examined for changes in quality of life using the St George’s Respiratory Questionnaire (SGRQ), symptoms, guideline-based care, and health care utilization.

Findings: Proactive iCare improved total SGRQ by 7–9 units (p < 0.0001), symptom SGRQ by 9 units (p<0.0001), activity SGRQ by 6–7 units (p<0.001) and impact SGRQ by 7–11 units (p<0.0001) at 3, 6 and 9 months compared with Usual Care. Proactive iCare increased the 6-minute walk distance by 40 m (p<0.001), reduced annual COPD-related urgent office visits by 76 visits per 100 participants (p<0.0001), identified unreported exacerbations, and decreased smoking (p=0.01). Proactive iCare also improved symptoms, the body mass index-airway obstruction-dyspnea-exercise tolerance (BODE) index and oxygen titration (p<0.05). Mortality in the Proactive iCare group (1.1%) was not significantly different than mortality in the Usual Care group (3.8%; p=0.08).

Interpretation: Linking integrated care with remote monitoring improves the lives of people with advanced COPD, findings that may have been made more relevant by the coronavirus 2019 (COVID-19) pandemic.

Citation

Citation: Koff KB, Min S, Diaz DLP, et al. Impact of Proactive Integrated Care on chronic obstructive pulmonary disease. J COPD F. 2021; 8(1): 100-116. doi: http://doi.org/10.15326/jcopdf.8.1.2020.0139

Keywords

primary care, disease management, patient education, acute exacerbations of COPD, telemedicine, self-care

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Author Affiliations

1. Division of Pulmonary, Critical Care and Sleep Medicine, Baylor Scott and White Health, Temple, Texas, United States

Address correspondence to:

Carl Boethal, MD
Department of Internal Medicine
Division of Pulmonary, Critical Care & Sleep Medicine
Scott & White Medical Center
Texas A & M University
2401 S. 31^st Street
Temple, TX 76508
Phone: 254-724-9887
Email: Carl.Boethel@BSWHealth.org

Abstract

Introduction: Hospital admissions and readmissions for chronic obstructive pulmonary disease (COPD) exacerbations are associated with increased mortality and higher cost. The management of exacerbations with a shortened course of systemic corticosteroids has similar efficacy as compared to longer steroid courses, but actual overall steroid dose given is still variable. The outcomes associated with steroid side effects, such as hyperglycemia, need further evaluation. We hypothesized that the use of higher doses of corticosteroids, and the subsequent hyperglycemia, contributes to readmission.

Methods: This is a retrospective study at a tertiary care referral center in central Texas between February 2014 and July 2016. Daily corticosteroid dose, blood glucose levels, and readmission rates at 30 and 31-90 days were recorded. Sample characteristics are described using descriptive statistics. A chi-square test or student’s t-test were used to test for associations in bivariate comparisons. Multivariable logistic regression assessed the association between readmission rate and demographic and clinical characteristics.

Results: There were 1120 patients admitted for COPD exacerbation between February 2014 and July 2016. A total of 57% were female, mean age was 69 years (standard deviation [SD] 12), and average body mass index (BMI) was 29.4 (SD 9.8). Of the total, 349 (31%) had diabetes prior to admission. The 30-day readmission rate was 16%, and the readmission rate from 31-90 days was 14%. The average prednisone equivalent dose per day during hospitalization was 86 mg (SD 52). A multivariable logistic regression model did not show any significant association between readmission and average daily glucose, high maximum glucose (>180 mg/dL on any reading), or prednisone equivalent administered per day.

Conclusion: Corticosteroid dose and hyperglycemia were not associated with an increased 30-day or 31-90-day readmission rate after COPD exacerbation discharge. In addition, using higher doses of corticosteroids instead of standard-of-care (prednisone 40 mg per day for a 5-day period) did not appear to affect the readmission rate in this cohort.

Citation

Citation: McGraw M, White HD, Boethel C, Zolfaghari K, Hochhalter A, Arroliga A.Corticosteroid dosing and glucose levels in COPD patients are not associated with increased readmissions. J COPD F. 2021; 8(1): 117-123. doi: http://doi.org/10.15326/jcopdf.8.1.2020.0172

Keywords

COPD, chronic obstructive pulmonary disease, readmission, corticosteroid dosing, hyperglycemia

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Click to read Corticosteroid Dosing and Glucose Levels in COPD Patients Are Not Associated with Increased Readmissions

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Author Affiliations

1. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, United States
2. Johns Hopkins Bayview Medical Center, Baltimore, Maryland, United States
3. Division of Pulmonary and Critical Care Medicine, Tri-Service General Hospital, Taipei, Taiwan
4. Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina, United States

**These authors share senior authorship

Address correspondence to:

Vickram Tejwani, MD
Email: tejwani@jhmi.edu
Phone: (443)287-3345

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is characterized by recurrent exacerbations. Macrophages play a critical role in immune response and tissue repair in COPD. Airway macrophages (AM) are exposed to environmental exposures which are retained in the cytoplasmic material. Both biomass and particulate matter have been linked to higher AM black carbon. It is unknown if AM black carbon is associated with COPD morbidity and macrophage phenotype.

Methods: Former smokers with COPD were enrolled and sputum induction was performed to obtain airway macrophages. Macrophages underwent black carbon quantification and flow cytometry phenotyping. Health information was obtained the same day as sputum induction and prospective exacerbations were assessed by monthly telephone calls.

Results: We studied 30 former smokers with COPD who had a mean age of 67 years and mean forced expiratory volume in 1 second (FEV₁)% predicted of 60.8%. Higher AM black carbon content was associated with increased total exacerbations and severe exacerbations and reduced CD80 expression.

Conclusion: AM black carbon association with respiratory morbidity is largely unexplored and this is the first study to identify association with prospective exacerbations. Macrophages expressed reduced CD80, a surface marker providing costimulatory signals required for development of antigen-specific immune responses. Our findings suggest that reduced CD80 expression is the pathophysiologic mechanism for the association of AM black carbon content and increased exacerbations. Therefore, beyond solely serving as a marker for increased exposures, AM black carbon content may be a predictor of future exacerbations given a macrophage less equipped to respond to an acute infectious exposure.

Citation

Citation: Tejwani V, Moughames E, Suresh K, et al. Black carbon content in airway macrophages is associated with reduced CD80 expression and increased exacerbations in former smokers with COPD. J COPD F. 2021; 8(1): 91-99. doi: http://doi.org/10.15326/jcopdf.8.1.2020.0170

Keywords

COPD, chronic obstructive pulmonary disease, macrophage, CD80, black carbon

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Click to read Black Carbon Content in Airway Macrophages is Associated with Reduced CD80 Expression and Increased Exacerbations in Former Smokers With COPD

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Author Affiliations

1. Department of Pneumology and Addictology, University of Montpellier, CHU Montpellier, Montpellier, France
2. Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, United States
3. Univ. Lyon, Université Claude-Bernard Lyon 1, Lyon, France
4. Hôpital de la Croix-Rousse, Service de Pneumologie, Hospices Civils de Lyon, Lyon, France
5. Division of Pulmonary, Allergy, and Critical Care Medicine, Lung Health Center, University of Alabama at Birmingham, Alabama, United States
6. College of Medicine and Health, University of Exeter Medical School, Exeter, United Kingdom
7. Pulmonary and Critical Care, University of Michigan, Ann Arbor, Michigan, United States
8. GlaxoSmithKline, Research Triangle Park, North Carolina, United States
9. Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
10. Department of Public Health, University of Copenhagen, Copenhagen, Denmark
11. Medical Department, Herlev University Hospital, Herlev, Denmark
12. GlaxoSmithKline, Stockley Park West, Uxbridge, Middlesex, United Kingdom
13. GlaxoSmithKline, Collegeville, Pennsylvania, United States
14. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
15. UCL Respiratory, University College London, London, United Kingdom
16. Respiratory Department, Hospital Universitario Quirónsalud Madrid, Universidad Europea de Madrid, Madrid, Spain
17. GlaxoSmithKline, Brentford, Middlesex, United Kingdom
18. University of Leicester, Leicester, United Kingdom
19. Weill Cornell Medicine, New York, New York, United States
20. GlaxoSmithKline, Paris, France
21. Midwest Chest Consultants, PC, St. Charles, Missouri, United States
22. The University of Manchester, Manchester University National Health Service Foundation Trust, United Kingdom
23. Division of Pulmonary, Allergy, and Critical Care, Columbia University Medical Center, New York, New York, United States
24. Pulmonary Research Institute at Lungen Clinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany
25. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
26. Section of Pulmonary and Critical Care Medicine, Airways Clinical Research Center, Baylor College of Medicine, Houston, Texas, United States

Address correspondence to:

Nicola A. Hanania, MD, MS
Airways Clinical Research Center Section of Pulmonary and Critical Care Medicine
Baylor College of Medicine
1504 Taub Loop, Houston, TX
Email: hanania@bcm.edu
Telephone: +1 713 873 3454

Abstract

Background: The InforMing the Pathway of COPD Treatment (IMPACT) trial demonstrated lower moderate/severe exacerbation rates with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI or UMEC/VI in patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. Since IMPACT was a global study, post-hoc analyses were conducted by geographic region to investigate potential differences in overall findings.

Methods: IMPACT was a 52-week, randomized, double-blind trial. Patients with symptomatic COPD and ≥1 moderate/severe exacerbation in the prior year were randomized 2:2:1 to once-daily FF/UMEC/VI 100/62.5/25µg, FF/VI 100/25µg, or UMEC/VI 62.5/25µg. Endpoints assessed in the overall, Western Europe and North America populations included on-treatment moderate/severe exacerbation (rates and time-to-first), trough forced expiratory volume in 1 second and St George’s Respiratory Questionnaire (SGRQ) total score. Safety was assessed.

Results: Overall, 10,355 patients were enrolled, 3164 from Western Europe, 2639 from North America. FF/UMEC/VI significantly reduced on-treatment moderate/severe exacerbation rates versus FF/VI and UMEC/VI in Western Europe (rate ratios 0.82 [95%CI 0.74-0.91], P<.001 and 0.76 [0.67-0.87], P<.001) and in North America (0.87 [0.77-0.97], P=.014 and 0.69 [0.60-0.80], P<.001). FF/UMEC/VI reduced time-to-first moderate/severe exacerbation and improved lung function versus FF/VI and UMEC/VI in both regions, and improved SGRQ total score in Western Europe, but not North America. Safety profiles were generally similar between treatment groups/regions; the inhaled corticosteroid class effect of increased pneumonia incidence was seen in North America but not Western Europe.

Conclusions: Consistent with intent-to-treat results, FF/UMEC/VI reduced moderate/severe exacerbation rate and risk and improved lung function in Western Europe and North America; however, between-regions differences were seen for SGRQ total score and pneumonia incidence.

Clinical Trial Registration: NCT02164513.

Citation

Citation: Bourdin A, Criner G, Devouassoux G, et al. Informing the pathway of COPD treatment (IMPACT) single-inhaler triple therapy (fluticasone furoate/umeclidinium/vilanterol) versus fluticasone furoate/vilanterol and umeclidinium/vilanterol in patients with COPD: analysis of the Western Europe and North America regions. J COPD F. 2021; 8(1): 76-90. doi: http://doi.org/10.15326/jcopdf.8.1.2020.0158

Keywords

COPD, exacerbations, single-inhaler triple therapy, Western Europe, North America

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Click to read InforMing the PAthway of COPD Treatment (IMPACT Trial) Single-Inhaler Triple Therapy (Fluticasone Furoate/Umeclidinium/Vilanterol) Versus Fluticasone Furoate/Vilanterol and Umeclidinium/Vilanterol in Patients With COPD: Analysis of the Western Europe and

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Author Affiliations

1. Department of Family and Community Health, University of Minnesota, Minneapolis, Minnesota, United States
2. COPD Foundation, Miami, Florida, United States
3. Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan, United States
4. Pulmonary Sciences and Critical Care Medicine, National Jewish Health, Denver, Colorado, United States
5. College of Public Health, Department of Preventive Medicine and Environmental Health, University of Kentucky, Lexington, Kentucky, United States
6. School of Public Health, University of Michigan, Ann Arbor, Michigan, United States
7. Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States
8. Evidera, Bethesda, Maryland, United States
9. Department of Family Medicine, Atrium Health, Charlotte, North Carolina, United States
10. Division of General Internal Medicine, Duke University Medical Center, Durham, North Carolina, United States
11. Medicine and Pulmonary and Critical Care, University of Illinois, Chicago, Illinois, United States
12. L.A. Net Community Health Center, Los Angeles, California, United States
13. Department of Family Medicine, University of Colorado, High Plains Research Network, Aurora, Colorado, United States
14. Division of Pulmonary and Critical Care Medicine, Columbia University, New York, New York, United States
15. Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, New York, United States

Address correspondence to:

Barbara Yawn
Email: yawnx002@umn.edu
Phone: (507) 261-3096

Abstract

Chronic obstructive pulmonary disease (COPD) often remains undiagnosed and untreated. To date, COPD screening/case finding has not been designed to identify clinically significant COPD, disease ready for therapies beyond smoking cessation. Herein, we describe the ongoing prospective, pragmatic cluster-randomized controlled trial to assess specificity and sensitivity of the COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE) tool consisting of 5 questions and peak expiratory flow. The tool is designed to identify clinically significant COPD (forced expiratory volume in 1 second [FEV₁] to forced vital capacity [FVC] ratio <.70 plus FEV₁% predicted <60% or increased risk for exacerbation) and the trial will explore the impact of CAPTURE-based screening on COPD diagnosis and treatment rates in primary care patients.

Of a total planned enrollment of 5000 English- or Spanish-speaking patients 45 to 80 years of age without a prior COPD diagnosis from 100 primary care practices, a total of 68 practices and 3064 patients have been enrolled in the study. Practices are centrally randomized to either usual care or clinician receipt of patient-level CAPTURE results. All clinicians receive basic COPD education with those in intervention practices also receiving CAPTURE interpretation education. In a single visit, patient participants complete a CAPTURE screening, pre- and post-bronchodilator spirometry and baseline demographic and health questionnaires to validate CAPTURE sensitivity, specificity, and predictive value of identifying undiagnosed, clinically significant COPD. One-year follow-up chart reviews and participant surveys assess the impact of sharing versus not sharing CAPTURE results with clinicians on clinical outcomes including level of respiratory symptoms and events and clinicians’ initiation of recommendation-concordant COPD care. This is one of the first U.S. studies to validate and assess impact of a simple COPD screening tool in primary care.

Citation

Citation: Yawn BP, Han M, Make BM, et al. Protocol summary of the COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE) validation in primary care study. J COPD F. 2021; 8(1): 60-75. doi: http://doi.org/10.15326/jcopdf.8.1.2020.0155

Keywords

COPD, chronic obstructive pulmonary disease, primary care, screening, Case finding, practice-based research networks, tool validation, CAPTURE study

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Click to read Protocol Summary of the COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE) Validation in Primary Care Study

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Author Affiliations

1. Division of Research, Kaiser Permanente Northern California, Oakland, California, United States
2. The Permanente Medical Group, Oakland, California, United States
3. Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States

Address correspondence to:

Laura Myers, MD, MPH
Division of Research
Kaiser Permanente Northern California
2000 Broadway
Oakland, CA 94612
Email: laura.c.myers@kp.org
Telephone: (925) 433-3491

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a common and costly reason for hospitalization and rehospitalization. The Hospital Readmissions Reduction Program penalizes hospitals for excess, non-elective, all-cause 30-day, inpatient rehospitalizations for COPD. We sought to determine how broadening the outcome definition would alter the numbers of patients being counted, specifically if observation stays and patients who died in the post-discharge period were included.

Methods: We performed a retrospective cohort study of patients hospitalized for COPD between July 1, 2010 and December 31, 2017 in 21 hospitals in the Kaiser Permanente Northern California health care system. We classified encounters into 3 outcomes groups based on a 30-day post-discharge observation period: Group (1) non-elective, all-cause, inpatient rehospitalizations, which is the current metric; Group (2) composite outcome of Group 1 or all-cause mortality; and Group (3) composite outcome of Group 1 or non-elective, all-cause, observation rehospitalization. We used the Box-Cox method to find the transformation of the cumulative curves that resulted in the smallest mean standard error. We used the slope of the transformed curve against days to test for significant differences between pairs of cumulative density curves.

Results: Of 1,384,025 hospitalizations, 11,304 encounters from 8097 patients met criteria to be index hospitalizations. The event rate for non-elective, all-cause, inpatient rehospitalizations was 17.1% (95% CI 10.4–26.5). The event rate for all-cause mortality was 4.7% (95% CI 3.1–7.7). The event rate for non-elective observation rehospitalizations was 3.9% (95% CI 1.7–7.0). The slope and standard error for Group 1 were 1.17 and 0.01, respectively, while the slope and standard error for Group 2 were 1.62 and 0.01, respectively (P=0.02 comparing Groups 1 and 2). The slope and standard error for Group 3 were 1.45 and 0.01, respectively (P=0.02 comparing Groups 1 and 3).

Conclusion: We show that adding outcomes such as mortality and observation rehospitalizations would change the counts of patients contributing to the Hospital Readmission Reduction Program penalty for COPD if the outcome were broadened. Including mortality or observation stays in the quality incentive program might incentivize hospitals and providers to prevent these events in addition to inpatient rehospitalizations.

Citation

Citation: Myers LC, Camargo C, Escobar G, Liu VX. Expanding post-discharge readmission metrics in patients with chronic obstructive pulmonary disease. J COPD F. 2021; 8(1): 54-59. doi: http://doi.org/10.15326/jcopdf.8.1.2020.0160

Keywords

chronic obstructive pulmonary disease, rehospitalizations, care quality

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Click to read Expanding Post-Discharge Readmission Metrics in Patients with Chronic Obstructive Pulmonary Disease

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Author Affiliations

1. Department of Medicine, Columbia University Irving Medical Center, New York, New York, United States
2. Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, United States
3. Kaiser Permanante San Francisco Medical Center, San Francisco, California, United States
4. Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center, New York, New York, United States

*Both authors contributed equally to the manuscript.

Address correspondence to:

R. Graham Barr, MD, DrPH
Columbia University Irving Medical Center
Presbyterian Hospital 9 East 105
630 West 168^th Street, New York, NY 10032
rgb9@columbia.edu

Abstract

Rationale: Studies suggest a pathogenic role of endothelial dysfunction in chronic obstructive lung disease (COPD). Omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation improves endothelial function in other diseases but has not been examined in COPD.

Objective: We hypothesized that n-3 PUFA supplementation would improve systemic endothelial function in COPD. We performed a pilot randomized, placebo-controlled, double-blind, phase 2 superiority trial (NCT00835289).

Methods: Adults with moderate and severe stable COPD (79% with emphysema on computed tomography [CT]) were randomized to high-dose fish oil capsules or placebo daily for 6 months. The primary endpoint was percentage change in brachial artery flow-mediated dilation (FMD) from baseline to 6 months. Secondary endpoints included peripheral arterial tonometry, endothelial microparticles (EMPs), 6-minute walk distance, respiratory symptoms, and pulmonary function.

Results: Thirty-three of 40 randomized participants completed all measurements. Change in FMD after 6 months did not differ between the fish oil and placebo arms (-1.1%, 95% CI -5.0—2.9, p=0.59). CD31⁺ EMPs increased in the fish oil arm (0.9%, 95% CI 0.1—1.7, p=0.04). More participants in the fish oil arm reported at least a 4-point improvement in the St George’s Respiratory Questionnaire (SGRQ) compared to placebo (8 versus 1; p=0.01). There were no significant changes in other secondary endpoints. There were 4 serious adverse events determined to be unrelated to the study (3 in the fish oil arm and 1 in the placebo arm).

Conclusion: Randomization to n-3 PUFAs for 6 months did not change systemic endothelial function in COPD. Changes in EMPs and SGRQ suggest n-3 PUFAs might have biologic and clinical effects that warrant further investigation.

Citation

Citation: Kim JS, Thomashow MA, Yip NH, et al. Randomization to omega-3 fatty acid supplementation and endothelial function in COPD: the COD-FISH randomized controlled trial. J COPD F. 2021; 8(1): 41-53. doi: http://doi.org/10.15326/jcopdf.8.1.2020.0132

Keywords

emphysema, chronic obstructive lung disease, fatty acid, endothelium

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Click to read Randomization to Omega-3 Fatty Acid Supplementation and Endothelial Function in COPD: The COD-Fish Randomized Controlled Trial

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Author Affiliations

1. Institut universitaire de cardiologie et de pneumologie de Québec – Université Laval, Québec, QC, Canada
2. Pneumology Department, Hospital Universitari Vall d´Hebron, Vall d´Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
3. CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain
4. Department of Molecular Medicine, Laval University, Quebec City, Canada

Address correspondence to:

Yohan Bossé, PhD
Professor, Université Laval
Department of Molecular Medicine
Canada Research Chair in Genomics of Heart and Lung Diseases
Institut universitaire de cardiologie et de pneumologie de Québec
Pavillon Marguerite-d'Youville, Y2106
2725, chemin Ste-Foy
Québec (Québec), Canada, G1V 4G5
Phone: 418-656-8711 ext. 3725
Email: yohan.bosse@criucpq.ulaval.ca

Abstract

Background: Alpha-1 antitrypsin deficiency (AATD) is caused by genetic variants in the SERPINA1 gene conferring risk of developing emphysema. The clinical expression of AATD-related emphysema mostly occurs in carriers of 2 deficient alleles. By DNA sequencing of SERPINA1, numerous rare variants have been identified. Clarifying whether 2 mutations observed in 1 patient are on the same or distinct alleles has obvious clinical implications.

Methods: We studied 7 carriers of a rare variant, Leu353Phe_fsTer24, known to lead to undetectable serum levels of AAT. Two of them were also carriers of the S or Z allele. We developed an allele-specific DNA sequencing method to characterize the allelic background of the Leu353Phe_fsTer24 variant.

Results: The Leu353Phe_fsTer24 variant was transmitted on the same allele as the M3 variant (E376D) in all patients. This mutation is thus named Q0_Ourém on the conventional PI system. We demonstrated that individuals harboring the E264V (S) and E342K (Z) mutations had them on distinct alleles from Q0_Ourém and are, thus, compound heterozygotes. The 7 Q0_Ourém carriers had AAT levels ranging from 0.18g/l to 0.82g/l. The lowest AAT serum levels were observed in compound heterozygotes (S/Q0_Ourém and Z/Q0_Ourém) suggesting higher risk of developing emphysema.

Conclusion: For the 7 patients, Leu353Phe_fsTer24 is transmitted on the M3 background and they are, thus, carriers of the Q0_Ourém allele. Allele-specific DNA sequencing was useful to distinguish 1 or 2 deficient alleles in carriers of 2 mutations. In rare cases, this method is important to understand the clinical significance of genetic variants found in SERPINA1.

Citation

Citation: Bellemare J, Gaudreault N, Valette K, et al. The clinical utility of determining the allelic background of mutations causing alpha-1 antitrypsin deficiency: the case with the null variant Q0(Mattawa)/Q0(Ourém). J COPD F. 2021; 8(1): 31-40. doi: http://doi.org/10.15326/jcopdf.8.1.2020.0168

Keywords

alpha-1 antitrypsin deficiency, null variants, allele-specific DNA sequencing, Q0(Ourém)

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Click to read The Clinical Utility of Determining the Allelic Background of Mutations Causing Alpha-1 Antitrypsin Deficiency: The Case with the Null Variant Q0(Mattawa)/Q0(Ourém)

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Author Affiliations

1. Value Evidence and Outcomes, GlaxoSmithKline plc., Brentford, United Kingdom
2. Patient Centred Outcomes, ICON plc., London, United Kingdom
3. Patient Centred Outcomes, ICON plc., Abingdon, United Kingdom
4. Value Evidence and Outcomes, GlaxoSmithKline plc., Uxbridge, United Kingdom
5. Global Respiratory Therapy Area, GlaxoSmithKline plc., Brentford, United Kingdom
6. Value Evidence and Outcomes, GlaxoSmithKline plc., Collegeville, Pennsylvania, United States
7. Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada

Address correspondence to:

Afisi S. Ismaila, PhD
Value Evidence and Outcomes
GlaxoSmithKline plc.
1250 South Collegeville Road
Collegeville, PA, USA 19426-0989
Phone: (919) 315 8229
E-mail: afisi.s.ismaila@gsk.com

Abstract

Background: A wide range of therapeutic regimens, including single-inhaler triple therapies (SITTs), are now available for the maintenance treatment of chronic obstructive pulmonary disease (COPD). Thus, an improved understanding of patient preferences may be valuable to inform physician prescribing decisions. This study was performed to assess the factors considered by patients when making decisions about their COPD treatments using qualitative techniques.

Methods: In the United Kingdom, United States and Germany, individual qualitative interviews (n=10 per country) and focus groups (1 per country; [United Kingdom, n=4; United States, n=6; Germany, n=6 participants]) were conducted. Interviews and focus groups were semi‑structured, lasting approximately 60 minutes, and focused on treatment preferences. Data were analyzed according to emerging themes identified from the interviews; qualitative thematic analysis of the data was performed using specialist software.

Results: In interviews and focus groups, efficacy, ease of use, and lower frequency of use were favored attributes for current treatment, while side effects, medication taste, and more complex administration techniques were key dislikes. In interviews, most participants would consider a switch in medication, mainly for improved efficacy, but also to reduce medication frequency or following physician advice. Overall, efficacy and ease of use were the 2 most important attributes reported in interviews in all 3 countries.

Conclusion: Patientswith COPD have preferences for certain attributes of medication, highlighting the multi-faceted nature of treatment effectiveness and the importance of the delivery device.These results were subsequently used to inform the design of a discrete choice experiment.

Citation

Citation: Schroeder M, Hall K, Eliasson L, et al. Treatment preferences of patients with chronic obstructive pulmonary disease: results from qualitative interviews and focus groups in the United Kingdom, United States, and Germany. J COPD F. 2021; 8(1): 19-30. doi: http://doi.org/10.15326/jcopdf.8.1.2020.0131

Keywords

chronic obstructive pulmonary disease (COPD), discrete choice experiment (DCE), interview, qualitative research, treatment preferences, focus group, multi-country

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Click to read Treatment Preferences of Patients with Chronic Obstructive Pulmonary Disease: Results from Qualitative Interviews and Focus Groups in the United Kingdom, United States, and Germany

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Author Affiliations

1. College of Public Health, University of Kentucky, Lexington, Kentucky, United States
2. College of Medicine, University of Kentucky, Lexington, Kentucky, United States
3. Department of Medicine, National Jewish Health, Denver, Colorado, United States
4. AlphaNet, Inc., Coral Gables, Florida, United States
5. Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical University of South Carolina, Charleston, South Carolina, United States

†deceased

Address correspondence to:

Radmila Choate, PhD, MPH
Department of Epidemiology
University of Kentucky College of Public Health
111 Washington Avenue
Lexington, KY 40536
Phone: 859-218-2237
E-mail: radmila.choate@uky.edu

Abstract

Background: The Step Forward Study (SFS) was designed to increase exercise activity and improve body mass index (BMI) among individuals with alpha-1 antitrypsin deficiency (AATD)-associated lung disease.

Methods: The SFS is a randomized trial of an intensive distance intervention that was delivered via a series of mailings and teleconferences versus no additional intervention. All participants (n=500) were also enrolled in a disease management program designed for individuals with AATD-associated lung disease who have been prescribed augmentation therapy. The primary outcome was self-reported number of exercise minutes per week. The secondary outcome was BMI. Linear mixed model analyses were used to assess the difference in average weekly exercise minutes between the intervention arms over time. T-tests, signed rank and Wilcoxon rank-sum tests were used to evaluate changes in BMI between the intervention arms and within each BMI category.

Results: The study included 429 individuals with evaluable primary outcome data.There was a significant effect of intervention on exercise minutes over time (p=0.018). Participants in the intervention group reported an average of 167.14 minutes (standard deviation [SD]=10.68) of weekly exercise and those in the standard care group reported 148.31 minutes (SD=10.96). There was a significant difference in BMI change between the intervention (mean BMI decrease 0.74, SD=2.16) and the standard care group (mean BMI decrease 0.27, SD=1.63); p=0.0122.

Conclusions: Individuals who were randomly assigned to the intervention group reported more exercise activity and improvements in BMI over the course of this multicomponent intervention compared to individuals assigned to standard care.

Citation

Citation: Choate R, Mannino DM, Holm KE, Beiko T, Boyd B, Sandhaus RA. Home-based multicomponent intervention increases exercise activity and improves body mass index: results of a 5-year randomized trial among individuals with alpha-1 antitrypsin deficiency-associated lung disease. J COPD F. 2021; 8(1): 7-18. doi: http://doi.org/10.15326/jcopdf.8.1.2020.0183

Keywords

alpha-1 antitrypsin deficiency, disease management, intensive distance intervention, Step Forward Study

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Click to read Home-Based Multicomponent Intervention Increases Exercise Activity and Improves Body Mass Index: Results of a 5-Year Randomized Trial Among Individuals with Alpha-1 Antitrypsin Deficiency-Associated Lung Disease

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Author Affiliations

1. Denver, Colorado

Address correspondence to:

Ron Balkissoon, MD, MSc, DIH, FRCPC
balkissoonr@njhealth.org

Abstract

This article does not contain an abstract.

Citation

Citation: Balkissoon R. Journal club—Severe acute respiratory syndrome coronavirus-2: impact on COPD patients. J COPD F. 2020; 7(4): 413-419. doi: http://doi.org/10.15326/jcopdf.7.4.2020.0188

Keywords

COPD, chronic obstructive pulmonary disease, COVID-19, SARS-CoV-2, coronavirus disease-2019, severe acute respiratory syndrome coronavirus-2

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Click to read Journal Club—Severe Acute Respiratory Syndrome Coronavirus-2: Impact on COPD Patients

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Author Affiliations

1. Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, University of Manchester, United Kingdom
2. The North West Lung Centre, Manchester University National Health Service Foundation Trust, Manchester, United Kingdom

Address correspondence to:

Professor Jørgen Vestbo
2^nd Floor, ERC Building
Wythenshawe Hospital
Southmoor Road
M23 9LT Manchester
United Kingdom
Phone: +45 3035 0317
Email: jorgen.vestbo@manchester.ac.uk

Abstract

This article does not contain an abstract.

Citation

Citation: Vesto J. Editorial: risk prediction in smokers. J COPD F. 2020; 7(4): 297-299. doi: http://doi.org/10.15326/jcopdf.7.4.2020.0174

Keywords

There are no keywords for this article.

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Click to read Editorial: Risk Prediction in Smokers

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Author Affiliations

1. Department of Pharmacy, University of Huddersfield, Huddersfield, United Kingdom and School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia
2. School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia
3. Lincoln Medical School, Universities of Nottingham and Lincoln, Lincolnshire, United Kingdom

Address correspondence to:

Chia Siang Kow, MPharm
School of Postgraduate Studies
International Medical University
Kuala Lumpur, Malaysia
Email: chiasiang_93@hotmail.com

Abstract

This article does not contain an abstract.

Citation

Citation: Hasan SS, Kow CS, Ahmadi K. Smoking cessation amid the coronavirus 2019 pandemic: making every contact count. J COPD F. 2020; 7(4): 300-302. doi: http://doi.org/10.15326/jcopdf.7.4.2020.0171

Keywords

smoking cessation, COVID-19, coronavirus disease 2019

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Click to read Smoking Cessation Amid the Coronavirus 2019 Pandemic: Making Every Contact Count

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Author Affiliations

1. Optimum Patient Care, Cambridge, United Kingdom
2. Observational and Pragmatic Research Institute, Singapore
3. Family Physician Airways Group of Canada, Stouffville, Ontario
4. University of Toronto, Toronto, Canada
5. University of Minnesota, Minneapolis, Minnesota, United States
6. COPD Foundation, Washington, DC, United States
7. Observational Pragmatic Research Institute, Singapore
8. General Practitioners Research Institute, Groningen, Netherlands
9. College of Medicine, University of Florida, Gainesville, Florida, United States
10. DARTNet Institute, Aurora, Colorado, United States
11. University at Buffalo, Buffalo, New York, United States
12. Boehringer Ingelheim, Ridgefield, Connecticut, United States
13. University of Michigan, Ann Arbor, Michigan, United States
14. Department of Medicine, National Jewish Health, Denver, Colorado, United States
15. University of Colorado, Denver, Colorado, United States
16. Thomas Jefferson University, Jenkintown, Pennsylvania, United States
17. Abington Jefferson Health, Jenkintown, Pennsylvania, United States
18. Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom

Address correspondence to:

Professor David B. Price
Academic Primary Care
Division of Applied Health Sciences
University of Aberdeen, Polwarth Building
Foresterhill, Aberdeen
AB25 2ZD, UK
Phone: +65 6962 3627
E-mail: dprice@opri.sg

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is commonly managed by family physicians, but little is known about specifics of management and how this may be improved. The Advancing the Patient Experience in COPD (APEX COPD) registry will be the first U.S. primary care, health system-based registry following patients diagnosed with COPD longitudinally, using a standardized set of variables to investigate how patients are managed in real life and assess outcomes of various management strategies.

Objective: Gaining expert consensus on a standardized list of variables to capture in the APEX COPD registry.

Methods: A modified, Delphi process was used to reach consensus on which data to collect in the registry from electronic health records (EHRs), patient-reported information (PRI) and patient-reported outcomes (PRO), and by physicians during subsequent office visits. The Delphi panel comprised 14 primary care and specialty COPD experts from the United States and internationally. The process consisted of 3 iterative rounds. Responses were collected electronically.

Results: Of the initial 195 variables considered, consensus was reached to include up to 115 EHR variables, 34 PRI/PRO variables and 5 office-visit variables in the APEX COPD registry. These should include information on symptom burden, diagnosis, COPD exacerbations, lung function, quality of life, comorbidities, smoking status/history, treatment specifics (including side effects), inhaler management, and patient education/self-management.

Conclusions: COPD experts agreed upon the core variables to collect from EHR data and from patients to populate the APEX COPD registry. Data will eventually be integrated, standardized and stored in the APEX COPD database and used for approved COPD-related research.

Citation

Citation: Edwards CL, Kaplan AG, Yawn BP, et al. Development of the Advancing the Patient Experience in COPD registry: a modified Delphi study. J COPD F. 2021; 8(1): 135-151. doi: http://doi.org/10.15326/jcopdf.8.1.2020.0154

Keywords

research, primary care, patient-reported outcomes, registry, clinically relevant data collection

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Click to read Development of the Advancing the Patient Experience in COPD Registry: A Modified Delphi Study

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Author Affiliations

1. Division of Pulmonary, Sleep and Critical Care Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
2. Department of Biostatistics, Department of Environmental Health, T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts

Address correspondence to:

Mary B. Rice, MD, MPH
Division of Pulmonary, Critical Care, and Sleep Medicine
Beth Israel Deaconess Medical Center
330 Brookline Ave KSB23
Boston, MA 02215
Phone: (617) 667-5864
Email: mrice1@bidmc.harvard.edu

Abstract

Despite clinical guidelines for chronic obstructive pulmonary disease (COPD) patients to self-treat worsening respiratory symptoms with supplemental inhaler/nebulizer use, few studies have investigated if symptom changes are associated with differences in oxygenation, lung function, or self-treatment. A total of 26 former smokers (mean age 72.7 ±7.5 years; 57.7% female) with COPD (≥ Global Initiative for Chronic Obstructive Lung Disease Stage 2) were followed for up to 4 months, during which they recorded daily oxygenation, lung function, and inhaler/nebulizer use. Differences in these health measures were assessed in association with self-reported worsening symptoms and COPD exacerbations, as defined by validated questionnaire. We collected 2451 observations with spirometry and questionnaire data and identified 253 symptom days (10.3%) and 47 (1.92%) exacerbation days. In linear mixed effects models adjusted for age, sex, race, height, weight, and season, each respiratory symptom reported worse than baseline was associated with a 0.19 percentage point (95% CI -0.31 to -0.07) lower daily oxygen saturation (p=0.002). On major symptom days (defined as worse-than-baseline dyspnea, sputum purulence or sputum amount), oxygen saturation was 0.56 percentage points lower (95% CI -0.89 to -0.23, p=0.001) than days without increased major symptoms. We found no association of symptom days or exacerbations with forced expiratory volume in 1 second. There were 8 reports of increased inhaler/nebulizer use from baseline on symptom days (1.5% of 253). In this moderate-to-severe COPD population, worsening respiratory symptoms were common and associated with lower oxygenation. However, participants did not self-treat symptoms with increased inhaler/nebulizer use, which may suggest poor perceived clinical benefit from short-acting bronchodilators and a potential target for patient education.

Citation

Citation: Sun WY, Zhang C, Synn AJ, Nurhussien L, Coull BA, Rice MB. Change in inhaler use, lung function and oxygenation in association with symptoms in COPD. J COPD F. 2020; 7(4): 404-412. doi: http://doi.org/10.15326/jcopdf.7.4.2020.0138

Keywords

FEV1, exacerbation, oxygenation, disease management, daily symptoms

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Click to read Change in Inhaler Use, Lung Function, and Oxygenation in Association with Symptoms in COPD

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Author Affiliations

1. Department of Medicine, University of North Carolina at Chapel Hill
2. Research, COPD Foundation, Washington, DC
3. College of Public Health, University of Kentucky, Lexington
4. School of Medicine, New York University, New York, New York
5. Pulmonary Disease and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota
6. Department of Pulmonary and Critical Care, School of Medicine, Oregon Health and Science University, Portland
7. Division of Mycobacterial and Respiratory Infections, National Jewish Health, Denver, Colorado
8. Icahn School of Medicine, Mt. Sinai West and Mt. Sinai St Luke’s Hospitals, Mt. Sinai, New York
9. Center for Chest Disease, Columbia College of Physicians and Surgeons, New York, New York
10. National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
11. University of Texas at Tyler
12. Center for Chest Disease, Mayo Clinic Florida, Jacksonville
13. Department of Medicine, University of Chicago, Chicago, Illinois
14. Division of Pulmonary and Critical Care Medicine, School of Medicine, University of Connecticut, Farmington
15. Georgetown University Medical Center, Washington, DC
16. University of Kansas Medical Center, Kansas City
17. Perelman School of Medicine, University of Pennsylvania, Philadelphia
18. Department of Infectious Disease, School of Medicine, Oregon Health and Science University School of Medicine, Portland

Address correspondence to:

Katherine A Despotes, MD
Phone: (919)649-0614
Email: katherine.despotes@unchealth.unc.edu

Abstract

Background: Increasing numbers of patients are being diagnosed with bronchiectasis, yet much remains to be elucidated about this heterogeneous patient population. We sought to determine the relationship between nutrition and health outcomes in non-cystic fibrosis (non-CF) bronchiectasis, using data from the U.S. Bronchiectasis Nontuberculous Mycobacterial Research Registry (U.S. BRR).

Methods: This was a retrospective, observational, longitudinal study using 5-year follow-up data from the BRR. Bronchiectasis was confirmed on computed tomography (CT). We stratified patients into nutrition categories using body mass index (BMI), and correlated BMI to markers of disease severity.

Results: Overall, n = 496 patients (mean age 64.6­ ± 13 years; 83.3% female) were included. At baseline 12.3% (n = 61) were underweight (BMI < 18.5kg/m²), 63.9% (n = 317) had normal weight (BMI ≥ 18.5kg/m² and <25.0kg/m²), 17.3% (n = 86) were overweight (BMI ≥ 25.0kg/m² and < 30.0kg/m²), and 6.5% (n= 32) were obese (BMI ≥ 30kg/m²). Men were overrepresented in the overweight and obese groups (25.6% and 43.8% respectively, p < 0.0001). Underweight patients had lower lung function (forced expiratory volume in 1 second [FEV₁] % predicted) than the other weight groups (64.5 ± 22, versus 73.5 ± 21, 68.5 ± 20, and 76.5 ± 21 in normal, overweight, and obese groups respectively, p = 0.02). No significant differences were noted between BMI groups for other markers of disease severity at baseline, including exacerbation frequency or hospitalization rates. No significant differences were noted in BMI distribution between patients with and without Pseudomonas, non-tuberculous mycobacteria, or by cause of bronchiectasis. The majority of patients demonstrated stable BMI over 5 years.

Conclusions: Although underweight patients with bronchiectasis have lower lung function, lower BMI does not appear to relate to other markers of disease severity in this patient population.

Citation

Citation: Despotes KA, Choate R, Addrizzo-Harris D, et al. J COPD F. 2020; 7(4): 390-403. doi: http://doi.org/10.15326/jcopdf.7.4.2020.0178

Keywords

bronchiectasis, BMI, nutrition, outcomes, U.S. Bronchiectasis Research Registry

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Click to read Nutrition and Markers of Disease Severity in Patients With Bronchiectasis

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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 (FEF_25-75) iso-volume FEF_25-75 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. J COPD F. 2020; 7(4): 382-389. doi: http://doi.org/10.15326/jcopdf.7.4.2020.0157

Keywords

early COPD, dual bronchodilator

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Click to read Design of the Redefining Therapy in Early COPD Study

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Author Affiliations

1. Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina, Chapel Hill
2. Marsico Lung Institute, University of North Carolina, Chapel Hill
3. Gillings School of Global Public Health, University of North Carolina, Chapel Hill
4. Division of Pulmonary, Critical Care, and Occupational Medicine, Carver College of Medicine, University of Iowa, Iowa City
5. Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama, Birmingham
6. Section of Pulmonary, Critical Care, Allergy, and Immunologic Disease, Wake Forest University, Winston-Salem, North Carolina
7. Division of Thoracic Medicine and Surgery, Temple University, Philadelphia, Pennsylvania
8. Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City
9. Division of Pulmonary Critical Care, Allergy, and Sleep Medicine, University of California, San Francisco
10. Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California, Los Angeles
11. Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine, University of Illinois, Chicago
12. Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor
13. Medicine Service, VA Ann Arbor Healthcare System, Ann Arbor, Michigan
14. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University Baltimore, Maryland

*A complete list of SPIROMICS collaborators is provided in the Acknowledgements section.

Address correspondence to:

Robert M. Burkes, MD
130 Mason Farm Rd, CB#7020
Chapel Hill, NC 27599
Phone: 919-966-2533
E-mail: burkesrt@ucmail.uc.edu

Abstract

Rationale: The antimicrobial peptide cathelicidin, also known in humans as LL-37, is a defensin secreted by immune and airway epithelial cells. Deficiencies in this peptide may contribute to adverse pulmonary outcomes in chronic obstructive pulmonary disease (COPD).

Objectives: Using clinical and biological samples from the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS), we assessed the associations of plasma cathelicidin levels with cross-sectional and longitudinal COPD outcomes.

Methods: A total of 1609 SPIROMICS participants with COPD and available plasma samples were analyzed. Cathelicidin was modeled dichotomously (lowest quartile [< 50 ng/ml] versus highest 75% [≥ 50 ng/ml]) and continuously per 10 ng/ml. Fixed-effect multilevel regression analyses were used to assess associations between cathelicidin and cross-sectional as well as longitudinal lung function. The associations between cathelicidin and participant-reported retrospective and prospective COPD exacerbations were assessed via logistic regression.

Measurements and Main Results: Cathelicidin < 50 ng/ml (N=383) was associated with female sex, black race, and lower body mass index (BMI).At baseline,cathelicidin < 50 ng/ml was independently associated with 3.55% lower % predicted forced expiratory volume in 1 second (FEV₁)(95% confidence interval [CI] -6.22% to -0.88% predicted; p=0.01), while every 10 ng/ml lower cathelicidin was independently associated with 0.65% lower % predicted FEV₁ (95% CI -1.01% to -0.28% predicted; p < 0.001). No independent associations with longitudinal lung function decline or participant-reported COPD exacerbations were observed.

Conclusions: Reduced cathelicidin is associated with lower lung function at baseline. Plasma cathelicidin may potentially identify COPD patients at increased risk for more severe lung disease.

Citation

Citation: Burkes RM, Ceppe AS, Couper DJ, et al. Plasma cathelicidin is independently associated with reduced lung function in COPD: analysis of the Subpopulations and Intermediate Outcome Measures In COPD Study Cohort. J COPD F. 2020; 7(4): 370-381. doi: http://doi.org/10.15326/jcopdf.7.4.2020.0142

Keywords

COPD, COPD outcomes, cathelicidin, immunology, innate immunity

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Click to read Plasma Cathelicidin is Independently Associated with Reduced Lung Function in COPD: Analysis of the Subpopulations and Intermediate Outcome Measures in COPD Study Cohort

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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. J COPD F. 2020; 7(4): 327-335. doi: http://doi.org/10.15326/jcopdf.7.4.2020.0144

Keywords

COPD, community-based palliative care, home-based palliative care, palliative care, experiences of palliative care

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

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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 PaCO_2­ 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. J COPD F. 2020; 7(4): 362-369. doi: http://doi.org/10.15326/jcopdf.7.4.2020.0137

Keywords

COPD, chronic obstructive pulmonary disease, high flow oxygen

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

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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. J COPD F. 2020; 7(4): 336-345. doi: http://doi.org/10.15326/jcopdf.7.4.2020.0176

Keywords

COPD, hypercapnia, National Emphysema Treatment Trial, NETT

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

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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. J COPD F. 2020; 7(4): 346-361. doi: http://doi.org/10.15326/jcopdf.7.4.2020.0146

Keywords

COPD, spirometry, COPDGene, PRISm, COPD Genetic Epidemiology study, preserved ratio-impaired spirometry, risk score

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

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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. J COPD F. 2020; 7(4): 315-326. doi: http://doi.org/10.15326/jcopdf.7.4.2020.0145

Keywords

COPD, chronic obstructive pulmonary disease, glycopyrrolate, eFlow, nebulized long-acting muscarinic antagonist, LAMA, metabolic syndrome

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

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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. J COPD F. 2020; 7(4): 303-314. doi: http://doi.org/10.15326/jcopdf.7.4.2020.0135

Keywords

cigarette smoking, industrial revolution, coal smoke, airway submucosal glands, airway mucosa

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Click to read A Brief History of Bronchitis in England and Wales

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Author Affiliations

1. Co-founder and Senior Medical Advisor, COPD Foundation, Washington, DC
2. Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University, New York, New York
3. Managing Editor, Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation, COPD Foundation, Washington, DC

Address correspondence to:

Byron Thomashow, MD
Email: bmt1@cumc.columbia.edu

Abstract

This article does not conatain abstract.

Citation

Citation: Thomashow B, Carlomagno CG. In gratitude to James D. Crapo. J COPD F. 2020; 7(3): 134-135. doi: http://doi.org/10.15326/jcopdf.7.3.2020.0177

Keywords

There are no keywords for this article.

Full Text

Click to read In Gratitude to James D. Crapo

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Author Affiliations

1. University Hospitals, Birmingham National Health Service Foundation Trust, Birmingham, United Kingdom
2. Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom

Address correspondence to:

Alice M. Turner, MBChB, PhD
Email: a.m.turner@bham.ac.uk
Phone +441213713885

Abstract

Environmental influences on clinical phenotype in alpha-1 antitrypsin deficiency (AATD) include cigarette smoke, occupational exposures, airway/sputum bacteria and outdoor air pollution. This narrative review describes the impact of the major environmental exposures and summarizes their effect on clinical phenotype and outcomes. In general, patients with AATD are more susceptible to pulmonary damage as a result of the relatively unopposed action of neutrophil elastase, in the context of neutrophilic inflammation stimulated by environmental factors. However, the amount of phenotypic variability explicable by environmental factors is insufficient to account for the wide range of clinical presentations observed, suggesting that a combination of genetic and environmental factors is likely to be responsible.

Citation

Citation: Rangaraju M, Turner AM. Why is disease penetration so variable in alpha-1 antitrypsin deficiency? The contribution of environmental factors. J COPD F. 2020; 7(3): 280-289. doi: http://doi.org/10.15326/jcopdf.7.3.2019.0177

Keywords

alpha-1 antitrypsin deficiency, cigarette smoking, air pollution, occupational exposure, microbiota

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Click to read Why is Disease Penetration so Variable in Alpha-1 Antitrypsin Deficiency? The Contribution of Environmental Factors

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Author Affiliations

1. Department of Molecular Medicine, Scripps Research, La Jolla, California
2. Pediatrics and Biochemistry, Saint Louis University, and Cardinal Glennon Children’s Medical Center, St. Louis, Missouri

^*These authors contributed equally as joint first authors

Address correspondence to:

William E. Balch, PhD
Department of Molecular Medicine
Scripps Research
La Jolla, California
Email: webalch@scripps.edu

Abstract

Deep medicine is rapidly moving towards a high-definition approach for therapeutic management of the patient as an individual given the rapid progress of genome sequencing technologies and machine learning algorithms. While considered a monogenic disease, alpha-1 antitrypsin (AAT) deficiency (AATD) patients present with complex and variable phenotypes we refer to as the “hallmarks of AATD” that involve distinct molecular mechanisms in the liver, plasma and lung tissues, likely due to both coding and non-coding variation as well as genetic and environmental modifiers in different individuals. Herein, we briefly review the current therapeutic strategies for the management of AATD. To embrace genetic diversity in the management of AATD, we provide an overview of the disease phenotypes of AATD patients harboring different AAT variants. Linking genotypic diversity to phenotypic diversity illustrates the potential for sequence-specific regions of AAT protein fold design to play very different roles during nascent synthesis in the liver and/or function in post-liver plasma and lung environments. We illustrate how to manage diversity with recently developed machine learning (ML) approaches that bridge sequence-to-function-to-structure knowledge gaps based on the principle of spatial covariance (SCV). SCV relationships provide a deep understanding of the genotype to phenotype transformation initiated by AAT variation in the population to address the role of genetic and environmental modifiers in the individual. Embracing the complexity of AATD in the population is critical for risk management and therapeutic intervention to generate a high definition medicine approach for the patient.

Citation

Citation: Wang C, Zhao P, Shuhong S, Teckman J, Balch WE. Leveraging population genomics for individualized correction of the hallmarks of alpha-1 antitrypsin deficiency. J COPD F. 2020; 7(3): 224-246. doi: http://doi.org/10.15326/jcopdf.7.3.2019.0167

Keywords

alpha-1 antitrypsin deficiency, phenotypes, genotypes, deep medicine, spatial covariance

Full Text

Click to read Leveraging Population Genomics for Individualized Correction of the Hallmarks of Alpha-1 Antitrypsin Deficiency

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Author Affiliations

1. Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida

Address correspondence to:

Adam Wanner, MD
Phone: (305) 243-3045
Email: AWanner@med.miami.edu

Abstract

This article does not contain an abstract.

Citation

Citation: Wanner A. Towards new therapeutic solutions for alpha-1 antitrypsin deficiency: role of the Alpha-1 Foundation. J COPD F. 2020; 7(3): 147-150. doi: http://doi.org/10.15326/jcopdf.7.3.2020.0141

Keywords

alpha-1 antitrypsin deficiency, AATD, therapeutic solutions, Alpha-1 Foundation

Full Text

Click to read Towards New Therapeutic Solutions for Alpha-1 Antitrypsin Deficiency: Role of the Alpha-1 Foundation

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Author Affiliations

1. Division of Gastroenterology and Hepatology, University Department of Medicine, Addenbrooke’s Hospital, Cambridge, United Kingdom
2. Department of Histopathology, Addenbrooke’s Hospital, Cambridge, United Kingdom
3. Department of Biology and Biotechnologies, Charles Darwin and Pasteur Institute Cenci-Bolognetti Foundation, Sapienza University of Rome, Rome, Italy
4. Department of Pathology, Cambridge University, Cambridge, United Kingdom
5. UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom

Address correspondence to:

Graeme Alexander, FRCP
Email: g.alexander@ucl.ac.uk
Phone: 44-207-256771

Abstract

Background: Alpha-1 antitrypsin deficiency (AATD) is an important, inherited cause of chronic liver disease. Marked variation in fibrosis stages in patients with homozygous deficiency and those factors that determine whether heterozygous carriers develop liver fibrosis, remain unexplained. Murine studies implicate polymerized alpha-1 antitrypsin (AAT) within hepatocytes as pathogenic.

Aims and Methods: The relationship between the quantity of polymerized AAT within hepatocytes (polymer load), stage of hepatic fibrosis and liver-related clinical outcomes (death, evolution to hepatocellular carcinoma, or need for liver transplantation) were investigated using liver tissue from 92 patients at first presentation with either homozygous or heterozygous AATD. Further tissue-based studies were undertaken to determine if polymerized AAT was associated with failure of cell cycle progression, accelerated aging or hepatocyte senescence by immunohistochemical analysis.

Results: The AAT polymer load correlated closely with hepatic fibrosis stage and long-term clinical outcome, independent of homozygous or heterozygous status. AAT polymers within hepatocytes correlated closely with failure of cell cycle progression assessed using cell cycle phase markers, accelerated aging manifest as shortened telomeres and other markers consistent with hepatocyte senescence manifest as the presence of nuclear p21 expression and enlarged nuclei. The proportion of p21 positive hepatocytes or hepatocytes with enlarged nuclei correlated with hepatic fibrosis stage and the long-term clinical outcome.

Conclusion: These data suggest that accumulation of AAT polymers within hepatocytes drives senescence. Quantitation of both the AAT polymer load or hepatocyte senescence markers correlated with hepatic fibrosis stage and the long-term clinical outcome. Either or both could be considered markers of disease severity and treatment response in clinical trials.

Citation

Citation: Mela M, Smeeton W, Davies SE, et al. The alpha-1 antitrypsin polymer load correlates with hepatocyte senescence, fibrosis stage and liver-related mortality. J COPD F. 2020; 7(3): 151-162. doi: http://doi.org/10.15326/jcopdf.7.3.2019.0158

Keywords

alpha-1 antitrypsin, liver fibrosis, polymers, polymer load, senescence

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Click to read The Alpha-1 Antitrypsin Polymer Load Correlates With Hepatocyte Senescence, Fibrosis Stage and Liver-Related Mortality

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Author Affiliations

1. National Heart and Lung Institute, Imperial College London, United Kingdom

Address correspondence to:

Omar S. Usmani
Imperial College
London United Kingdom
Phone: 0044 207 351 8943
E-mail: o.usmani@imperial.ac.uk

Abstract

Inhalation therapy is integral in the management of patients with chronic obstructive pulmonary disease (COPD). Specifically, intravenous augmentation therapy is available to patients with alpha-1 antitrypsin deficiency (AATD), although there is insufficient alpha-1 antitrypsin (AAT) delivery to the lungs to modify airways inflammation. In contrast, the inhaled route allows replacement therapy to reach the target site of action and with higher AAT levels. Patients certainly support the inhalation route as an alternative to intravenous injections, obviating repetitive needle insertion and allowing treatment empowerment rather than dependency on traveling to specialized units. The difficulty with inhalation has been the ability to target the formulation to the pathophysiological site of disease: the emphysematous lung parenchyma of the small alveolated airways. Recent advances have suggested nebulizers as being able to deliver an adequate dose, consistently and reproducibly, and, coupled with developments in formulation science, allowed replacement therapy to reach the epithelial lining fluid of the small airways. The bench science has been translated to the first randomized, placebo-controlled clinical trial to study the effects of nebulized AAT, which, although not meeting the primary endpoint of prolonging time to first exacerbation, showed this treatment modality was safe and achievable in a large patient cohort. Indeed, learning from this trial suggests the importance of choosing the right clinical endpoints, and recent key advances in lung physiology indices allow better assessment of the “silent zone” of small airways disease. Knowledge from other respiratory diseases will complement treating patients with AATD, where there is considerable innovation in aerosol science and inhalation medicine directed at utilizing the inhaled route. Indeed, it could be postulated that the inhaled route may not only achieve local pulmonary therapeutic benefit, but through systemic absorption and controlled pharmacokinetic profiling, the formulation may reach and treat liver disease.

Citation

Citation: Usmani OS. Feasibility of aerosolized alpha-1 antitrypsin as a therapeutic option. J COPD F. 2020; 7(3): 272-279. doi: http://doi.org/10.15326/jcopdf.7.3.2019.0179

Keywords

COPD, aerosol, inhaler, therapeutic, small airways

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Click to read Feasibility of Aerosolized Alpha-1 Antitrypsin as a Therapeutic Option

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Author Affiliations

1. Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
2. Coordinating Center for Alpha-1 Antitrypsin Deficiency-Related Liver Disease of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER) and the European Association for the Study of the Liver (EASL) Registry Group “Alpha-1 Liver”

Address correspondence to:

Pavel Strnad, MD
European Reference Network on Hepatological Diseases
European Association for the Study of the Liver Registry Group
University Hospital Aachen
Aachen, Germany
Email: pstrnad@ukaachen.de
Phone: +49 241 80-35324

Abstract

Alpha-1 antitrypsin deficiency (AATD) is a systemic disorder affecting mainly the lung and the liver and is caused by mutations in SERPINA1, the AAT gene. A homozygous “Pi*Z” mutation (Pi*ZZ genotype) may cause liver fibrosis on its own independently of pulmonary AATD manifestation, while heterozygous Pi*Z carriage (Pi*MZ genotype) is considered a strong risk factor for development of liver cirrhosis in patients with concomitant liver disease such as alcoholic and non-alcoholic liver disease. In Pi*ZZ homozygotes, liver disease constitutes the second leading cause of death and is highly heterogeneous. About 35% of Pi*ZZ individuals display significant liver fibrosis on biopsy (i.e., fibrosis stage ≥ 2 on scale 0–4). Among non-invasive methods for liver fibrosis assessment, liver stiffness measurement (LSM) via vibration-controlled transient elastography (VCTE) has been most widely evaluated. Based on these data, Pi*ZZ adults have 20x increased odds of developing advanced liver fibrosis (i.e., fibrosis stage ≥ 3) than adults without AAT mutation. Risk factors for accelerated fibrosis progression are male sex, age ≥ 50 years, alcohol misuse, obesity, diabetes mellitus, or metabolic syndrome. Unlike VCTE, other ultrasound- and magnetic resonance-based elastography methods have been assessed in small cohorts of Pi*ZZ individuals and remain to be comprehensively validated. Among blood-based fibrosis tests, AST-to-platelet ratio index (APRI) correlates moderately with histologic fibrosis stage and LSM. Given APRI’s wide availability, it can be used for risk stratification as an adjunct to LSM or when LSM is not at hand. Despite recent efforts, AATD-related liver disease, especially for genotypes other than Pi*ZZ, remains greatly understudied. AATD individuals should be offered liver biochemistry, liver ultrasound, and non-invasive fibrosis assessment at the time of diagnosis to detect potential complications and for proper risk stratification. If signs of AATD-related liver disease occur (i.e., pathologic fibrosis test or repeatedly elevated liver enzymes), patients should be referred to a health care center specialized in AATD-related liver disease and be screened for potentially treatable comorbidities. To exclude the latter, they may need a liver biopsy. Moreover, every health care provider of an AATD individual should be aware of the potential liver manifestation, counsel their patient on modifiable hepatic risk factors, and offer them regular liver check-ups.

Citation

Citation: Hamesch K, Strnad P. Non-invasive assessment and management of liver involvement in adults with alpha-1 antitrypsin deficiency. J COPD F. 2020; 7(3): 260-271. doi: http://doi.org/10.15326/jcopdf.7.3.2019.0161

Keywords

alpha-1 antitrypsin deficiency, AATD, liver fibrosis, liver stiffness, elastography, SERPINA1, genetic liver disease, rare liver disease

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Click to read Non-Invasive Assessment and Management of Liver Involvement in Adults With Alpha-1 Antitrypsin Deficiency

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Author Affiliations

1. Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom

Address correspondence to:

Elizabeth Sapey, MD
Email: E.sapey@bham.ac.uk
Phone: ++44 121 472 2000.

Abstract

Neutrophils have been implicated in the pathogenesis of alpha-1 antitrypsin deficiency (AATD) since the first descriptions of the disease. Neutrophil proteinases can cause all lung manifestations of AATD, from small airways destruction, to emphysema, to chronic bronchitis and airflow obstruction. Initially, it was proposed that neutrophil functions were normal in AATD, responding in an initially physiological manner to a high burden of pulmonary inflammation. More recent studies have shed new light on this, describing changes in neutrophil responses (a modulation of usual cellular functions) in the presence of inflammation or infection which might enhance tissue damage while impeding bacterial clearance, providing some evidence to support there being an AATD neutrophil phenotype.

Many facets of neutrophil function in AATD can be explained by the loss of alpha-1 antitrypsin (AAT) in diverse biological processes. If this were the only reason for altered neutrophil functions, one would predict similar disease presentation across affected people. However, this is not the case. Despite similar (low) levels of AAT, lung disease is extremely variable in AATD, with some patients suffering a significant burden of lung disease and some much less, irrespective of smoking habits and, in some cases, despite augmentation therapy. This review will explore how complex neutrophil responses are and how they are altered with age, inflammation and AATD. Further, it will discuss the need to understand more completely which aspects of AATD-associated disease are driven by neutrophils and how patients more susceptible to neutrophil dysfunction could be identified to potentially stratify treatment approaches.

Citation

Citation: Sapey E.Neutrophil modulation in alpha-1 antitrypsin deficiency. J COPD F. 2020; 7(3): 247-259. doi: http://doi.org/10.15326/jcopdf.7.3.2019.0164

Keywords

COPD, emphysema, chronic obstructive pulmonary disease, exacerbations, alpha-1 antitrypsin deficiency, proteinases, bronchitis

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Click to read Neutrophil Modulation in Alpha-1 Antitrypsin Deficiency

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Author Affiliations

1. Channing Division of Network Medicine and Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, Massachusetts

Address correspondence to:

Brian D Hobbs, MD, MMSc
phone: 617-525-2140
email: brian.hobbs@channing.harvard.edu

Abstract

Individuals with alpha-1 antitrypsin deficiency (AATD) have marked heterogeneity in lung function, suspected to be related to a combination of both environmental (e.g., cigarette smoking) and genetic factors. Lung function is heritable in the general population and in persons with severe AATD. Several genetic modifiers of lung function in persons with AATD have been described; however, replication is lacking. A genome-wide association study (GWAS) of lung function in persons with AATD has yet to be performed and may inform whether genetic determinants of lung function are overlapping in persons with AATD and in the general population. As GWASs require large sample sizes for adequate power, genetic risk scores offer an alternate approach to assess the overlap of genetic determinants of lung function in the general population in persons with AATD. Where GWASs are limited to common genetic variant discovery, whole genome sequencing (for rare variant discovery) and integrative genomic studies (examining the influence of genetic variants on gene, protein, and metabolite levels) offer potential for an expanded discovery of genetic modifiers of lung function in AATD. In the following review we examine past descriptions of genetic modifiers of lung function in AATD and describe a path forward to further investigate and define the likely genetic modifiers of lung function in AATD.

Citation

Citation: Hobbs BD, Cho MH. Why is disease penetration so variable? Role of genetic modifiers of lung function in alpha-1 antitrypsin deficiency. J COPD F. 2020; 7(3): 214-223. doi: http://doi.org/10.15326/jcopdf.7.3.2019.0159

Keywords

COPD, chronic obstructive pulmonary disease, alpha-1 antitrypsin deficiency, lung function, genetic modifiers, heterogeneity

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Click to read Why is Disease Penetration So Variable? Role of Genetic Modifiers of Lung Function in Alpha-1 Antitrypsin Deficiency

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Author Affiliations

1. Department of Internal Medicine, Temple University Health System, Philadelphia, Pennsylvania
2. Department of Thoracic Medicine and Surgery, Temple University Health System, Philadelphia, Pennsylvania

*These authors contributed equally as first authors. A list of individuals in the Temple University COVID-19 Research Group is provided in the online data supplement.

Address correspondence to:

Stephanie Tittaferrante, MD
Department of Internal Medicine and Surgery
Temple University Health System
Philadelphia, Pennsylvania
Email: stephanie.tittaferrante@tuhs.temple.edu

Abstract

This article does not contain an abstract.

Citation

Citation: Tittaferrante S, Gupta R, Kim V, Temple University Research Group. Thoracic computed tomography features of coronavirus disease 2019 patients with emphysema. J COPD F. 2020; 7(3): 290-296. doi: http://doi.org/10.15326/jcopdf.7.3.2020.0166

Keywords

emphysema, COVID-19, coronavirus disease 2019, computed tomography imaging, CT scans

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Click to read Thoracic Computed Tomography Features of Coronavirus Disease 2019 Patients with Emphysema

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Author Affiliations

1. Irish Centre for Genetic Lung Disease, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland.

Address correspondence to:

Emer P. Reeves, PhD
Irish Centre for Genetic Lung Disease
Royal College of Surgeons in Ireland
Education and Research Centre
Beaumont Hospital
Dublin 9, Ireland
Email: emerreeves@rcsi.ie
Phone: +35318093877

Abstract

For many years, the lung disease associated with alpha-1 antitrypsin (AAT) deficiency (AATD) was perceived as being secondary to an imbalance between this serine protease inhibitor and the target protease, neutrophil elastase (NE). More recently, a greater understanding of the pathways leading to lung inflammation has shed light on new potential attributes and presented AATD as an inflammatory condition in which proteases and neutrophils still play a major role, but in which pro-inflammatory cytokines, either induced by the actions of NE or by other pro-inflammatory processes normally modulated by AAT, are involved. In this review, we will look at the various cytokines centrally involved in AATD lung disease, and how a greater understanding of their contribution may help development of targeted therapies.

Citation

Citation: McElvaney OF, Murphy MP, Reeves EP, McElvaney NG. Anti-cytokines as a strategy in alpha-1 antitrypsin deficiency. J COPD F. 2020; 7(3): 203-213. doi: http://doi.org/10.15326/jcopdf.7.3.2019.0171

Keywords

inflammation, cytokines, alpha-1 antitrypsin, neutrophils, interleukin-8

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Author Affiliations

1. Department of Respiratory Medicine, Hannover Medical School, Member of German Centre for Lung Research (DZL), Hannover, Germany; Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland

Address correspondence to:

Sabina Janciauskiene, PharmD, PhD
Phone: +49 511 532 7297
Email: janciauskiene.sabina@mh-hannover.de

Abstract

Reactive oxygen and nitrogen species can be generated endogenously (by mitochondria, peroxisomes, and phagocytic cells) and exogenously (by pollutions, UV exposure, xenobiotic compounds, and cigarette smoke). The negative effects of free radicals are neutralized by antioxidant molecules synthesized in our body, like glutathione, uric acid, or ubiquinone, and those obtained from the diet, such as vitamins C, E, and A, and flavonoids. Different microelements like selenium and zinc have no antioxidant action themselves but are required for the activity of many antioxidant enzymes. Furthermore, circulating blood proteins are suggested to account for more than 50% of the combined antioxidant effects of urate, ascorbate, and vitamin E. Antioxidants together constitute a mutually supportive defense against reactive oxygen and nitrogen species to maintain the oxidant/antioxidant balance. This article outlines the oxidative and anti-oxidative molecules involved in the pathogenesis of chronic obstructive lung disease. The role of albumin and alpha-1 antitrypsin in antioxidant defense is also discussed.

Citation

Citation: Janciauskiene S. The beneficial effects of antioxidants in health and diseases. J COPD F. 2020; 7(3): 182-202. doi: http://doi.org/10.15326/jcopdf.7.3.2019.0152

Keywords

inflammation, alpha-1 antitrypsin, oxidative stress, reactive oxygen species, antioxidants, lung disease

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Click to read The Beneficial Effects of Antioxidants in Health and Diseases

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Author Affiliations

1. COPD Foundation, Research Department, Washington, DC
2. University of Minnesota, Family and Community Health, Minneapolis
3. Pulmonary and Critical Care, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
4. Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University, New York, New York

Address correspondence to:

Ruth Tal-Singer, PhD
Email: rtalsinger@copdfoundation.org
Phone: 610-570-4876

Abstract

This article does not contain an abstract.

Citation

Citation: Tal-Singer R, Yawn B, Wise B, Thomashow B, Boyce DM. The COPD Foundation Coronavirus Disease 2019 International Medical Experts Survey: results. J COPD F. 2020; 7(3): 139-146. doi: http://doi.org/10.15326/jcopdf.7.3.2020.0164

Keywords

COVID-19, coronavirus disease 2019, medical experts, steroids, discharge

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Click to read The COPD Foundation Coronavirus Disease 2019 International Medical Experts Survey: Results

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Author Affiliations

1. David Geffen School of Medicine, University of California, Los Angeles

Address correspondence to:

Donald P. Tashkin, MD
Email: dtashkin@mednet.ucla.edu

Abstract

This article does not contain an abstract.

Citation

Citation: Tashkin DP, Barjaktarevic IZ. Nebulized treatments and the possible risk of coronoavirus transmission: where is the evidence? J COPD F. 2020; 7(3): 136-138. doi: http://doi.org/10.15326/jcopdf.7.3.2020.0161

Keywords

COVID-19, coronavirus disease 2019, SARS-CoV-2, nebulized treatments, severe acute respiratory syndrome coronavirus 2

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Click to read Nebulized Treatments and the Possible Risk of Coronavirus Transmission: Where Is the Evidence?

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Author Affiliations

1. National Institute of Health and Medical Research (INSERM), National Center for Scientific Research (CNRS), University Bordeaux, Bordeaux Research In Translational Oncology, BaRITOn, Bordeaux, France

Address correspondence to:

Marion Bouchecareilh, PhD
INSERM U1053 BaRITon
Bat 1A 2eme étage
146, Rue Léo Saignat
33076 Bordeaux, France
Phone: +33(0)557571607
Email: marionb@ibgc.cnrs.fr / marion.bouchecareilh@inserm.fr

Abstract

Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disease caused by mutations in the SERPINA1 gene and is associated with a decreased level of circulating alpha-1 antitrypsin (AAT). Among all the known mutations in the SERPINA1 gene, homozygous for the Z allele is well-known to result in both lung and liver disease. Unlike the lung injury that occurs in adulthood with the environment (notably, tobacco) as a co-factor, the hepatic damage is more complicated. Despite a common underlying gene mutation, the liver disease associated with AATD presents a considerable variability in the age-of-onset and severity, ranging from transient neonatal cholestasis (in early childhood) to cirrhosis and liver cancer (in childhood and adulthood). Given that all the cofactors– genetics and/or environmental– have not been fully identified, it is still impossible to predict which individuals with AATD may develop severe liver disease. The discovery of these modifiers represents the major challenge for the detection, diagnosis, and development of new therapies to provide alternative options to liver transplantation. The aim of this current review is to provide an updated overview of our knowledge on why some AATD patients associated with liver damage progress poorly.

Citation

Citation: Bouchecareilh M. Alpha-1 antitrypsin deficiency-mediated liver toxicity: why do some patients do poorly? What do we know so far? J COPD F. 2020; 7(3): 172-181. doi: http://doi.org/10.15326/jcopdf.7.3.2019.0148

Keywords

alpha-1 antitrypsin deficiency, liver disease, modifiers, genetic factors

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Click to read Alpha-1 Antitrypsin Deficiency-Medicated Liver Toxicity: Why Do Some Patients Do Poorly? What Do We Know So Far?

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Author Affiliations

1. Lung Investigation Unit, University Hospitals, Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom

Address correspondence to:

Professor Robert A. Stockley
Lung Investigation Unit
University Hospitals Birmingham NHS Foundation Trust
Queen Elizabeth Hospital Birmingham
Edgbaston, Birmingham,
United Kingdom
Email: rob.stockley@uhb.nhs.uk
Telephone: +44 121 3716808

Abstract

Alpha-1 antitrypsin deficiency (AATD) has traditionally been associated with the development of early onset panlobular emphysema thought to reflect the direct interstitial damage caused by neutrophil elastase. Since this enzyme is highly sensitive to irreversible inhibition by alpha-1 antitrypsin (AAT), the logic of intravenous augmentation therapy has remained unquestioned and efficacy is supported by both observational studies and formal clinical trials. However, evidence suggests that although AAT augmentation modulates the progression of emphysema, it only slows it down. This raises the issue of whether our long-held beliefs of the cause of the susceptibility to develop emphysema in deficient individuals are correct. There are several aspects of our understanding of the disease that might benefit from a radical departure from traditional thought. This review addresses these concepts and alternative pathways that may be central to progression of emphysema.

Citation

Citation: Stockley RA. Alpha-1 antitrypsin deficiency: have we got the right proteinase? J COPD F. 2020; 7(3): 163-171. doi: http://doi.org/10.15326/jcopdf.7.3.2019.0151

Keywords

emphysema, alpha-1 antitrypsin deficiency, small airways disease, proteinases, oxidants

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Click to read Alpha-1 Antitrypsin Deficiency: Have We Got the Right Proteinase?

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Author Affiliations

1. Cleveland Clinic Lerner College of Medicine of Case Western Reserve School of Medicine, Cleveland, Ohio
2. University of Colorado Anschutz Medical Campus, Aurora
3. National Jewish Health, Denver, Colorado
4. Brigham and Women's Hospital, Boston, Massachusetts

Address correspondence to:

James D. Crapo, MD
National Jewish Health
Email: crapoj@njhealth.org

Abstract

This article does not contain an abstract.

Citation

Citation: Lowe KE, Hokanson JE, Make BJ, et al. Letter to editor: response by authors. J COPD F. 2020; 7(2): 82-85. doi: http://doi.org/10.15326/jcopdf.7.2.2020.0152

Keywords

There are no keywords for this article.

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Click to read Letter to the Editor: Response by Authors

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