Chronic Obstructive Pulmonary Diseases:Journal of the COPD Foundation

Volume 10, Issue 3 - 2023

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

Original Research:

Impact of Bronchiectasis on COPD Severity and Alpha-1 Antitrypsin Deficiency as a Risk Factor in Individuals with a Heavy Smoking History

Manuel Izquierdo, DO1 Chad R. Marion, DO, PhD1 Frank Genese, DO2 John D. Newell, MD3 Wanda K. O'Neal, PhD4 Xingnan Li, PhD5 Gregory A. Hawkins, PhD6 Igor Barjaktarevic, MD, PhD7 R. Graham Barr, MD, PhD8 Stephanie Christenson, MD9 Christopher B. Cooper, MD, PhD7 David Couper, PhD10 Jeffrey Curtis, MD11,12 Meilan K. Han, MD, MS12 Nadia N. Hansel, MD, MPH13 Richard E. Kanner, MD14 Fernando J. Martinez, MD, MS15 Robert Paine, III, MD14 Vickram Tejwani, MD16 Prescott G. Woodruff, MD, MPH9 Joe G. Zein, MD, PhD16 Eric A. Hoffman, PhD3 Stephen P. Peters, MD, PhD1 Deborah A. Meyers, PhD5 Eugene R. Bleecker, MD5 Victor E. Ortega, MD, PhD17 for the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) investigators.

Author Affiliations

  1. Section on Pulmonary, Critical Care, Allergy and Immunological Diseases, Wake Forest School of Medicine, Wake Forest, North Carolina, United States
  2. Department of Pulmonary Disease, Rochester General Hospital, Rochester, New York, United States
  3. Departments of Radiology, Medicine, and Biomedical Engineering, University of Iowa, Iowa City, Iowa, United States
  4. Marisco Lung Institute, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  5. Department of Medicine, University of Arizona, Tucson, Arizona, United States
  6. Center for Precision Medicine, Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States
  7. Department of Medicine, David Geffen School of Medicine, Los Angeles, California, United States
  8. Columbia University Medical Center, New York City, New York, United States
  9. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California, United States
  10. Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States
  11. VA Ann Arbor Healthcare System, Ann Arbor, Michigan, United States
  12. Division of Pulmonary and Critical Care Medicine, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, United States
  13. School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
  14. Division of Respiratory, Critical Care, and Occupational Pulmonary Medicine, Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, United States
  15. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medical College of Cornell University, New York City, New York, United States
  16. Respiratory Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States
  17. Department of Internal Medicine, Division of Respiratory Diseases, Center for Individualized Medicine, Mayo Clinic, Scottsdale, Arizona, United States

Address correspondence to:

Victor E. Ortega, MD, PhD
Division of Respiratory Diseases
Department of Internal Medicine
Center for Individualized Medicine
Mayo Clinic
13400 E. Shea Boulevard
Scottsdale, Arizona
Email: Ortega.Victor@mayo.edu
Phone: (480) 301-9432

Abstract

Rationale: Bronchiectasis is common among those with heavy smoking histories, but risk factors for bronchiectasis, including alpha-1 antitrypsin deficiency, and its implications for COPD severity are uncharacterized in such individuals.

Objectives: To characterize the impact of bronchiectasis on COPD and explore alpha-1antitrypsin as a risk factor for bronchiectasis.

Methods: SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) participants (N=914; ages 40–80 years; ≥20-pack-year smoking) had high-resolution computed tomography (CT) scans interpreted visually for bronchiectasis, based on airway dilation without fibrosis or cicatrization. We performed regression-based models of bronchiectasis with clinical outcomes and quantitative CT measures. We deeply sequenced the gene encoding -alpha-1 antitrypsin, SERPINA1, in 835 participants to test for rare variants, focusing on the PiZ genotype (Glu366Lys, rs28929474).

Measurements and Main Results: We identified bronchiectasis in 365 (40%) participants, more frequently in women (45% versus 36%, p=0.0045), older participants (mean age=66[standard deviation (SD)=8.3] versus 64[SD=9.1] years, p=0.0083), and those with lower lung function (forced expiratory volume in 1 second [FEV1 ] percentage predicted=66%[SD=27] versus 77%[SD=25], p<0.0001; FEV1 to forced vital capacity [FVC] ratio=0.54[0.17] versus 0.63[SD=0.16], p<0.0001). Participants with bronchiectasis had greater emphysema (%voxels ≤-950 Hounsfield units, 11%[SD=12] versus 6.3%[SD=9], p<0.0001) and parametric response mapping functional small airways disease (26[SD=15] versus 19[SD=15], p<0.0001). Bronchiectasis was more frequent in the combined PiZZ and PiMZ genotype groups compared to those without PiZ, PiS, or other rare pathogenic variants (N=21 of 40 [52%] versus N=283 of 707[40%], odds ratio [OR]=1.97; 95% confidence interval [CI]=1.002, 3.90, p=0.049), an association attributed to White individuals (OR=1.98; 95%CI = 0.9956, 3.9; p=0.051).

Conclusions: Bronchiectasis was common in those with heavy smoking histories and was associated with detrimental clinical and radiographic outcomes. Our findings support alpha-1antitrypsin guideline recommendations to screen for alpha-1 antitrypsin deficiency in an appropriate bronchiectasis subgroup with a significant smoking history.

Citation

Citation: Izquierdo M, Marion CR, Genese F, et al; for the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) investigators. Impact of bronchiectasis on COPD severity and alpha-1 antitrypsin deficiency as a risk factor in individuals with a heavy smoking history. Chronic Obstr Pulm Dis. 2023; 10(3): 199-210. doi: http://dx.doi.org/10.15326/jcopdf.2023.0388

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Impact of Coronavirus Disease 2019 on Hospital Admissions, Health Status, and Behavioral Changes of Patients with COPD

Eva Pappe, MD1 Ralf Hammerich, MD2 Jacopo Saccomanno, MD1 Thomas Sgarbossa, MD1 Anne Pohrt, PhD3 Bernd Schmidt, MD4 Christian Grah, MD5 Stephan Eisenmann, MD6 Angelique Holland, MD7 Stephan Eggeling, MD8 Franz Stanzel, MD9 Martin Witzenrath, MD1 Ralf-Harto Hübner, MD1

Author Affiliations

  1. Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany
  2. Administrative Office for Clinical Quality and Risk Management, Charité-Universitätsmedizin Berlin, Berlin, Germany
  3. Institute of Biometry and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, Berlin, Germany
  4. Department of Respiratory Medicine, DRK Kliniken Berlin Mitte, Berlin, Germany
  5. Department of Internal Medicine and Respiratory Medicine, Clinic Havelhöhe Berlin, Berlin, Germany
  6. Department of Internal Medicine I, Pulmonary Medicine, University Hospital Halle (Saale), Germany
  7. Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University Marburg, Marburg, Germany
  8. Department of Thoracic Surgery, Vivantes Netzwerk für Gesundheit, Klinikum Neukölln, Berlin, Germany
  9. Lungenklinik Hemer, Hemer, Germany

Address correspondence to:

Eva Pappe, MD
Charitéplatz 1
10117
Berlin, Germany
Phone: 0049 30 450 653078
E-mail: eva.pappe@charite.de

Abstract

Introduction: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of acquiring severe coronavirus disease 2019 (COVID-19), which is why self-isolation was recommended. However, long periods of social isolation, accompanied by limited access to health care systems, might influence the outcome of patients with severe COPD negatively.

Methods: Data from COPD and pneumonia patients at Charité-Universitätsmedizin Berlin and the volume of endoscopic lung volume reduction (ELVR) surgeries from the German Lung Emphysema Registry (Lungenemphysem Register e.V.) were analyzed from pre-pandemic (2012 to 2019) to the pandemic period (2020 and 2021). In addition, 52 patients with COPD Global initiative for chronic Obstructive Lung Disease (GOLD) stage 4 status included in the lung emphysema registry received questionnaires during lockdowns from June 2020 to April 2021.

Results: Admissions and ventilation therapies administered to COPD patients significantly decreased during the COVID-19 pandemic. Likewise, there was a reduction in ELVR treatments and follow-ups registered in German emphysema centers. Mortality was slightly higher among patients hospitalized with COPD during the pandemic. Increasing proportions of COPD patients with GOLD stage 3 and GOLD stage 4 status reported behavioral changes and subjective feelings of increasing COPD symptoms the longer the lockdown lasted. However, COPD symptom questionnaires revealed stable COPD symptoms over the pandemic time period.

Summary: This study reveals reduced COPD admissions and elective treatment procedures of COPD patients during the pandemic, but a slight increase in mortality among patients hospitalized with COPD, irrespective of COVID-19. Correspondingly, patients with severe COPD reported subjective deterioration of their health status, probably caused by their very strict compliance with lockdown measures.

Citation

Citation: Pappe E, Hammerich R, Saccomanno J, et al. Impact of coronavirus disease 2019 on hospital admissions, health status, and behavioral changes of patients with COPD. Chronic Obstr Pulm Dis. 2023; 10(3): 211-223. doi: http://dx.doi.org/10.15326/jcopdf.2022.0383

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Understanding the Patient Experience of Home-Based Pulmonary Rehabilitation with Health Coaching for COPD: A Qualitative Interview Study

William R. Midthun, BA1 Maria V. Benzo, MD1 Jennifer L. Ridgeway, PhD2,3 Roberto P. Benzo, MD, MS1

Author Affiliations

  1. Mindful Breathing Laboratory, Division of Pulmonary, Critical Care and Sleep Medicine, Mayo Clinic, Rochester, Minnesota, United States
  2. Division of Health Care Delivery Research, Mayo Clinic, Rochester, Minnesota, United States
  3. Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota, United States

Address correspondence to:

Roberto Benzo, MD, MS
Mindful Breathing Laboratory
Mayo Clinic
200 First St SW
Rochester, MN 55902
Email: benzo.roberto@mayo.edu

Abstract

Background: We recently reported on a randomized trial of home-based pulmonary rehabilitation (PR) for chronic obstructive pulmonary disease (COPD) that showed improvement in all domains of quality of life, accelerometry-measured physical activity, and self-management. In this current study, we used a theoretical framework to help us gain an in-depth understanding of how patients experience complex, multi-component programs to help uncover factors related to behavior change and to inform program scale-up in other populations.

Study Design and Methods: The parent trial was conducted with COPD patients receiving care at an academic medical center and a community health system in the upper Midwest. The 12-week PR intervention included 3 daily video-guided exercises, activity monitors, and weekly telephonic health coaching. Trial participants were eligible to participate in an individual phone interview about their experience if they completed the intervention within the prior 12 months.. Analysis of verbatim transcripts followed an inductive thematic approach followed by deductive categorization and interpretation using a theoretical model: the Capability, Opportunity, Motivation–Behavior (COM-B) model developed for linking intervention functions to aspects of behavioral change.

Results: Among 32 eligible program participants,32 were approached, and 15 completed interviews between October 19, 2021, and January 13, 2022. The COM-B model and recommendations for program improvement were observed in the primary findings.

Discussion: Participants’ feedback highlighted how the health coaching bolstered skills and confidence among individuals with the poorest function at program enrollment and how improved physical function and mood led to motivation. It also highlighted the roles of technology and telephonic support in a home-based program. Suggestions for improvement included providing exercise variations.

Citation

Citation: Midthun WR, Benzo MV, Ridgeway JL, Benzo RP. Understanding the patient experience of home-based pulmonary rehabilitation with health coaching for COPD: a qualitative interview study. Chronic Obstr Pulm Dis. 2023; 10(3): 224-233. doi: http://dx.doi.org/10.15326/jcopdf.2022.0384

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Impact of Marijuana Smoking on COPD Progression in a Cohort of Middle-Aged and Older Persons

Igor Barjaktarevic, MD, PhD1 Christopher B. Cooper, MD1 Tracie Shing, DrPH2 Russell G. Buhr, MD, PhD1,3 Eric A. Hoffman, PhD4 Prescott G. Woodruff, MD, MPH5 M. Bradley Drummond, MD, MHS6 Richard E. Kanner, MD7 MeiLan K. Han, MD, MS8 Nadia N. Hansel, MD9 Russell P. Bowler, MD, PhD10 Gregory L. Kinney, MPH, PhD11 Sean Jacobson, MS11 Madeline A. Morris, MPH12 Fernando J. Martinez, MD, MS13 Jill Ohar, MD14 David Couper, PhD2 Donald P. Tashkin, MD1

Author Affiliations

  1. Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States
  2. Collaborative Studies Coordinating Center, Department of Biostatistics, Gilling’s School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States
  3. Center for the Study of Healthcare Innovation, Implementation, and Policy, Health Services Research and Development, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California, United States
  4. Departments of Radiology, Medicine and Bioengineering, University of Iowa, Iowa City, Iowa, United States
  5. Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, California, United States
  6. Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States
  7. Division of Respiratory, Critical Care, and Occupational Pulmonary Medicine, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, Utah, United States
  8. Division of Pulmonary and Critical Care Medicine, School of Medicine, University of Michigan, Ann Arbor, Michigan, United States
  9. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, United States
  10. Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colorado, United States
  11. Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  12. College of Nursing and Health Sciences, University of Vermont, Burlington, Vermont, United States
  13. Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, New York, New York, United States
  14. Division of Pulmonary, Critical Care, Allergy and Immunology, School of Medicine, Wake Forest University, Wake Forest, North Carolina, United States

Address correspondence to:

Donald P. Tashkin, MD
Division of Pulmonary and Critical Care Medicine
David Geffen School of Medicine
University of California at Los Angeles
10833 Le Conte Ave.
Los Angeles, CA 90095 USA
Phone: (310) 825-3163
E-mail: dtashkin@mednet.ucla.edu

Abstract

Background: Limited data are available regarding marijuana smoking’s impact on the development or progression of chronic obstructive pulmonary disease (COPD) in middle-aged or older adults with a variable history of tobacco cigarette smoking.

Methods: We divided ever-tobacco smoking participants in the SubPopulations and InteRmediate Outcomes In COPD Study (SPIROMICS) into 3 groups based on self-reported marijuana use: current, former, or never marijuana smokers (CMSs, FMSs or NMSs, respectively). Longitudinal data were analyzed in participants with ≥2 visits over a period of ≥52 weeks.

Measurements: We compared CMSs, FMSs, and NMSs, and those with varying amounts of lifetime marijuana use. Mixed effects linear regression models were used to analyze changes in spirometry, symptoms, health status, and radiographic metrics; zero-inflated negative binomial models were used for exacerbation rates. All models were adjusted for age, sex, race, baseline tobacco smoking amount, and forced expiratory volume in 1 second (FEV1) %predicted.

Results: Most participants were followed for ≥4 years. Annual rates of change in FEV1, incident COPD, respiratory symptoms, health status, radiographic extent of emphysema or air trapping, and total or severe exacerbations were not different between CMSs or FMSs versus NMSs or between those with any lifetime amount of marijuana use versus NMSs.

Conclusions: Among SPIROMICS participants with or without COPD, neither former nor current marijuana smoking of any lifetime amount was associated with evidence of COPD progression or its development. Because of our study’s limitations, these findings underscore the need for further studies to better understand longer-term effects of marijuana smoking in COPD.

Citation

Citation: Barjaktarevic I, Cooper CB, Shing T, et al. Impact of marijuana smoking on COPD progression in a cohort of middle-aged and older persons. Chronic Obstr Pulm Dis. 2023; 10(3): 234-247. doi: http://dx.doi.org/10.15326/jcopdf.2022.0378

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Clinical Use of an Exposure, Symptom, and Spirometry Algorithm to Stratify Smokers into COPD Risk Phenotypes: A Case-Finding Study Combined with Smoking Cessation Counseling

Abraham Bohadana, MD1 Ariel Rokach, MD1 Pascal Wild, PhD2 Ofir Kotek, MD3 Chen-Chen Shuali, MD1 Hava Azulai, MD1 Gabriel Izbicki, MD1

Author Affiliations

  1. Respiratory Research Unit, Pulmonary Institute, Department of Medicine, Shaare Zedek Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
  2. PW Statistical Consulting, Laxou, France
  3. Hadassah School of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel

Address correspondence to:

Abraham B. Bohadana, MD
Pulmonary Institute
Shaare Zedek Medical Center
12 Bayit Street
91031
Jerusalem, Israel
Email: abohadana@szmc.org.il
Phone: 972-2-6555111

Abstract

Background: Chronic obstructive pulmonary disease (COPD) case-finding aims to detect airflow obstruction in symptomatic smokers and ex-smokers. We used a clinical algorithm including smoking, symptoms, and spirometry to classify smokers into COPD risk phenotypes. In addition, we evaluated the acceptability and effectiveness of including smoking cessation advice in the case-finding intervention.

Methods: Smoking, symptoms, and spirometry abnormalities (airflow obstruction: forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] <0.7 or preserved-ratio spirometry (FEV1<80% of predicted value and FEV1/FVC ratio ≥ 0.7)[ were assessed in a group of 864 smokers aged ≥ 30 years. The combination of these parameters allowed the identification of 4 phenotypes: Phenotype A (no symptoms, normal spirometry; reference), Phenotype B (symptoms; normal spirometry; possible COPD), Phenotype C (no symptoms; abnormal spirometry; possible COPD), and Phenotype D (symptoms; abnormal spirometry; probable COPD). We assessed phenotype differences in clinical variables and modeled the trend from phenotype A to phenotype D. Smoking cessation advice based on spirometry was provided. Follow-up was done by telephone 3 months later.

Results: Using smokers without symptoms or abnormal spirometry (phenotype A; n=212 ]24.5%[) as a reference, smokers were classified into possible COPD (phenotype B;n=332 ]38.4%[; and C: n=81 ]9.4%[) and probable COPD (phenotype D: n=239 ]27.2%[). The trend from baseline phenotype A to probable COPD phenotype D was significant for the number of cigarettes/day and the number of years of smoking (p=0.0001). At follow-up, 58 (7.7%) of the respondents (n=749) reported that they had quit smoking.

Conclusions: Our clinical algorithm allowed us to classify smokers into COPD phenotypes whose manifestations were associated with smoking intensity and to significantly increase the number of smokers screened for COPD. Smoking cessation advice was well accepted, resulting in a low but clinically significant quit rate.

]

Citation

Citation: Bohadana A, Rokach A, Wild P, et al. Clinical use of an exposure, symptom, and spirometry algorithm to stratify smokers into COPD risk phenotypes: a case-finding study combined with smoking cessation counseling. Chronic Obstr Pulm Dis. 2023; 10(3): 248-258. doi: http://dx.doi.org/10.15326/jcopdf.2022.0368

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The Experiences of Individuals with a History of Acute Exacerbations of COPD and Their Thoughts on Death: Empirical Qualitative Research

Yasemin Ceyhan, PhD, RN1

Author Affiliations

  1. Department of Internal Medicine-Nursing, Faculty of Health Sciences, Kirsehir Ahi Evran University, Kirsehir, Turkey

Address correspondence to:

Yasemin Ceyhan, PhD, RN 3rd Floor
Bagbasi Campus Faculty of Health Sciences
Kirşehir, Turkey
Phone:+90 546 459 80 65
E-mail: yasemin-ceyhan@hotmail.com

Abstract

Background: The most important problem of chronic obstructive pulmonary disease (COPD) patients is acute exacerbation. Researching this experience and examining its relationship with death is extremely important in patient care.

Methods: This study was conducted to reveal the experiences of individuals with a history of acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) and their thoughts on death by qualitative empirical research. The study was conducted in a pulmonology clinic between July and September 2022. In-depth face-to-face interviews were conducted with patients in their rooms using a semi-structured form created specifically for the study and used as a data collection tool. With patient consent, interviews were recorded and documented. During the data analysis phase, the Colaizzi method was used. The study was presented in accordance with the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist for qualitative research.

Results: The study was completed with 15 patients. A total of 13 of the patients were male and the mean age was 65 years. Patient statements were coded after the interviews and collected under 11 sub-themes. These sub-themes were categorized under the following main themes: recognizing AECOPDs, AECOPD instant experiences, post-AECOPD, and thoughts on death.

Conclusion: Patients were able to recognize the symptoms of an AECOPD, that the severity of the symptoms increased during the exacerbation, that they felt regret or anxiety about re-exacerbation, and that all of these factors contributed to their fear of death.

Citation

Citation: Ceyhan Y. The experiences of individuals with a history of acute exacerbations of COPD and their thoughts on death: empirical qualitative research. Chronic Obstr Pulm Dis. 2023; 10(3): 259-269. doi: http://dx.doi.org/10.15326/jcopdf.2023.0389

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Changes in Lung Volumes with Spirometric Disease Progression in COPD

Mehrdad Arjomandi, MD1,2 Siyang Zeng, MS1,3 Jianhong Chen, MS1,2 Surya P. Bhatt, MD4 Fereidoun Abtin, MD5 Igor Barjaktarevic, MD, PhD5 R. Graham Barr, MD, PhD6 Eugene R. Bleecker, MD7 Russell G. Buhr, MD, PhD5 Gerard J. Criner, MD8 Alejandro P. Comellas, MD9 David J. Couper, PhD10 Jeffrey L. Curtis, MD11,12 Mark T. Dransfield, MD4 Spyridon Fortis, MD9 MeiLan K. Han, MD, MS11 Nadia N. Hansel, MD, MPH13 Eric A. Hoffman, PhD 9 John E. Hokanson, MPH, PhD14 Robert J. Kaner, MD15 Richard E. Kanner, MD16 Jerry A. Krishnan, MD, PhD 17 Wassim W. Labaki, MD, MS11 David A. Lynch, MD18 Victor E. Ortega, MD, PhD19 Stephen P. Peters, MD, PhD20 Prescott G. Woodruff, MD, MPH2 Christopher B. Cooper, MD5 Russell P. Bowler, MD, PhD21 Robert Paine III, MD, PhD16,21 Stephen I. Rennard, MD22 Donald P. Tashkin, MD6 and the COPDGene and SPIROMICS Investigators.

Author Affiliations

  1. San Francisco Veterans Affairs Healthcare System, San Francisco, California, United States
  2. Department of Medicine, University of California, San Francisco, California, United States
  3. Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, Washington, United States
  4. University of Alabama at Birmingham, Birmingham, Alabama, United States
  5. Department of Medicine, University of California, Los Angeles, California, United States
  6. Columbia-Presbyterian Medical Center, New York, New York, United States
  7. University of Arizona, College of Medicine, Tucson, Arizona, United States
  8. Temple University, Philadelphia, Pennsylvania, United States
  9. University of Iowa, Iowa City, Iowa, United States
  10. University of North Carolina, Chapel Hill, North Carolina, United States
  11. Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States
  12. Medical Service, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan, United States
  13. Department of Medicine, Johns Hopkins University, Baltimore, United States
  14. Department of Epidemiology, School of Public Health, University of Colorado, United States
  15. Weill Cornell Medical Center, New York, New York, United States
  16. University of Utah, Salt Lake City, Utah, United States
  17. University of Illinois at Chicago, Chicago, Illinois, United States
  18. Department of Radiology, National Jewish Health Systems, Denver, Colorado, United States
  19. Mayo Clinic, Scottsdale, Arizona, United States
  20. Wake Forest School of Medicine, Winston-Salem, North Carolina, United States
  21. Department of Medicine, National Jewish Health Systems, Denver, Colorado, United States
  22. University of Nebraska Medical Center, Omaha, Nebraska, United States

Address correspondence to:

Mehrdad Arjomandi, MD
Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine
University of California, San Francisco
San Francisco Veterans Affairs Medical Center
Building 203, Room 3A-128, Mailstop 111-D
4150 Clement Street, San Francisco, CA 94121
Phone: (415) 221-4810 x24393
Email: mehrdad.arjomandi@ucsf.edu

Abstract

Background: Abnormal lung volumes representing air trapping identify the subset of smokers with preserved spirometry who develop spirometric chronic obstructive pulmonary disease (COPD) and adverse outcomes. However, how lung volumes evolve in early COPD as airflow obstruction develops remains unclear.

Methods: To establish how lung volumes change with the development of spirometric COPD, we examined lung volumes from the pulmonary function data (seated posture) available in the U.S. Department of Veterans Affairs electronic health records (n=71,356) and lung volumes measured by computed tomography (supine posture) available from the COPD Genetic Epidemiology (COPDGene®) study (n=7969) and the SubPopulations and InterMediate Outcome Measures In COPD Study (SPIROMICS) (n=2552) cohorts, and studied their cross-sectional distributions and longitudinal changes across the airflow obstruction spectrum. Patients with preserved ratio-impaired spirometry (PRISm) were excluded from this analysis.

Results: Lung volumes from all 3 cohorts showed similar patterns of distributions and longitudinal changes with worsening airflow obstruction. The distributions for total lung capacity (TLC), vital capacity (VC), and inspiratory capacity (IC) and their patterns of change were nonlinear and included different phases. When stratified by airflow obstruction using Global initiative for chronic Obstructive Lung Disease (GOLD) stages, patients with GOLD 1 (mild) COPD had larger lung volumes (TLC, VC, IC) compared to patients with GOLD 0 (smokers with preserved spirometry) or GOLD 2 (moderate) disease. In longitudinal follow-up of baseline GOLD 0 patients who progressed to spirometric COPD, those with an initially higher TLC and VC developed mild obstruction (GOLD 1) while those with initially lower TLC and VC developed moderate obstruction (GOLD 2).

Conclusions: In COPD, TLC, and VC have biphasic distributions, change in nonlinear fashions as obstruction worsens, and could differentiate those GOLD 0 patients at risk for more rapid spirometric disease progression.

Citation

Citation: Arjomandi M, Zeng S, Chen J, et al; COPD and SPIROMICS investigators. Changes in lung volumes with spirometric disease progression in COPD. Chronic Obstr Pulm Dis. 2023; 10(3): 270-285. doi: http://dx.doi.org/10.15326/jcopdf.2022.0363

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Associations of Smoking, Cytomegalovirus Serostatus, and Natural Killer Cell Phenotypes in Smokers With and At Risk for COPD

Robert M. Burkes, MD, MSCR1,2 Elijah Bailey, BS1 Timothy Hwalek, MD1 Andrew Osterburg, PhD1 Laura Lach, MS2 Ralph Panos, MD2 Stephen N. Waggoner, PhD3,4 Michael T. Borchers, PhD1,2

Author Affiliations

  1. Division of Pulmonary, Critical Care and Sleep Medicine, College of Medicine, University of Cincinnati, Cincinnati, Ohio, United States
  2. Department of Veterans Affairs, Cincinnati VA Hospital, Cincinnati, Ohio, United States
  3. Center for Autoimmune Genomics and Etiology, Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  4. Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio, United States

Address correspondence to:

Robert M. Burkes, MD, MSCR
Division of Pulmonary, Critical Care and Sleep Medicine
Department of Internal Medicine
University of Cincinnati College of Medicine
P.O. Box 45267-0564
Cincinnati, Ohio 45267
Email: burkesrt@ucmail.uc.edu
Phone: (513)558-7296

Abstract

Introduction: Chronic obstructive disease (COPD) risk factors, smoking, and chronic infection (cytomegalovirus [CMV]) may mold natural killer (NK) cell populations. What is not known is the magnitude of the effect CMV seropositivity imparts on populations of smokers with and at risk for COPD. We investigate the independent influence of CMV seropositivity on NK cell populations and differential effects when stratifying by COPD and degree of smoking history.

Methods: Descriptive statistics determine the relationship between cytotoxic NK cell populations and demographic and clinical variables. Multivariable linear regression and predictive modeling were performed to determine associations between positive CMV serology and proportions of CD57+ and natural killer group 2C (NKG2C)+ NK cells. We dichotomized our analysis by those with a heavy smoking history and COPD and described the effect size of CMV seropositivity on NK cell populations.

Results: When controlled for age, race, sex, pack-years smoked, body mass index, and lung function, CMV+ serostatus was independently associated with a higher proportion of CD57+, NKG2C+, and NKG2C+CD57+ NK cells. CMV+ serostatus was the sole predictor of larger NKG2C+ and CD57+NKG2C+ populations. Associations are more pronounced in those with COPD and heavy smokers.

Conclusion: Among Veterans who are current and former smokers, CMV+ serostatus was independently associated with larger CD57+ and NKG2C+ populations, with a larger effect in heavy smokers and those with COPD, and was the sole predictor for increased expression of NKG2C+ and CD57+NKG2C+ populations. These findings may be broadened to include the assessment of longitudinal NK cell population change, accrued inflammatory potential, and further identification of pro-inflammatory NK cell population clusters.

Citation

Citation: Burkes RM, Bailey E, Hwalek T, et al. Associations of smoking, cytomegalovirus serostatus, and natural killer cell phenotypes in smokers with and at risk for COPD. Chronic Obstr Pulm Dis. 2023; 10(3): 286-296. doi: http://dx.doi.org/10.15326/jcopdf.2022.0382

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Structured Evaluation and Management of Patients with COPD in an Accredited Program

Mandeep Singh, MD1 En Shuo Hsu, BA2 Efstathia Polychronopoulou, PhD2 Gulshan Sharma, MD, MPH1 Alexander G. Duarte, MD1

Author Affiliations

  1. Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States
  2. Office of Biostatistics, University of Texas Medical Branch, Galveston, Texas, United States

Address correspondence to:

Alexander Duarte, MD
Division of Pulmonary, Critical Care, and Sleep Medicine
University of Texas Medical Branch
301 University Blvd.
Galveston, TX 77555
Phone: (409) 772-2436
Email: aduarte@utmb.edu

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is an ambulatory care-sensitive condition.

Methods: We compared the impact of care received by patients with COPD at Joint Commission-accredited, disease-specific clinics and primary care clinics at an academic health care systemfrom April 2014 to March 2018. Patients with COPD ≥ 40 years old with ≥ 2 outpatient visits 30 days apart were identified. Baseline demographics, disease-specific performance measures, and health care utilization were compared between groups. Propensity matching was conducted and time to the first emergency department (ED) visit and hospitalization was performed using Cox regression analysis.

Results: Of 4646 unique patients with COPD, 1114 were treated at disease-specific clinics and 3532 at primary care clinics. The entire group was predominantly female (58.8 %), non-Hispanic White (74.2 %) with a mean age of 65.4 ± 11.4 years consisting of current (47.6 %) or former smokers (38.4 %). In the disease-specific group, performance measures were performed more frequently, and lower rates of ED visits (hazard ratio [HR]=0.31, 95% confidence interval [CI] 0.18–0.54) and hospitalizations (HR 0.41, 95% CI 0.21–0.79) noted in comparison to the primary care group.

Conclusion: In this observational study, the implementation of achronic disease management program through accredited disease-specific clinics for patients with COPD was associated with reduced all-cause ED visits and hospitalizations.

Citation

Citation: Singh M, Hsu ES, Polychronopoulou E, Sharma G, Duarte AG. Structured evaluation and management of patients with COPD in an accredited program. Chronic Obstr Pulm Dis. 2023; 10(3): 297-307. doi: http://dx.doi.org/10.15326/jcopdf.2022.0366

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Augmentation Therapy Modulates Systemic Inflammation in Individuals with Alpha-1 Antitrypsin Deficiency and Chronic Obstructive Pulmonary Disease

Jorge E. Lascano, MD1 Leonard Riley, MD2 Nazli Khodayari, PhD1 Mark L. Brantly, MD1

Author Affiliations

  1. University of Florida, Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Gainesville, Florida, United States
  2. Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Kansas City Veterans Affairs Medical Center, Kansas City, Missouri, United States

Address correspondence to:

Jorge Lascano, MD
1600 SW Archer Road PO Box 100225
Gainesville, Florida 32610
Phone: (352) 273-8740
Email: Jorge.lascano@medicine.ufl.edu

Abstract

Background: Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder that leads to chronic obstructive pulmonary disease (COPD) and lower circulating levels of AAT, which is a protease inhibitor with potent anti-inflammatory effects. In order to better understand the presence of systemic inflammation in AAT-deficient individuals with COPD, we investigatedthe plasma levels of C-reactive protein (CRP).

Methods: AAT-deficient individuals and a matched cohort with a normal AAT genotype were recruited from the Alpha-1 Foundation DNA and Tissue Bank. AAT genotypes were determined by a combination of a Taqman-based assay. AAT and CRP levels were determined by nephelometry. Comparisons were determined by unpaired t-test and standard Pearson’s correlation.

Results: Our study included 40 control participants and 742 AAT-deficient participants, of which 498 received augmentation therapy. In the AAT-deficient participants, the plasma AAT was 20.2±11.6µM and 4.5±1.3µM (P<0.0001) with and without augmentation therapy, respectively, and the CRP was 0.32±0.53mg/dL and 0.69±1.97mg/dL (P=0.0169), respectively. There was a negative correlation between the percentage predicted of forced expiratory volume in 1 second and CRP in the group not receiving augmentation therapy (r=−0.2528, P<0.05), and there was no correlation in participants receiving augmentation therapy.

Conclusion: Compared to healthy individuals, AAT-deficient individuals with COPD have higher levels of circulating CRP, suggesting increased systemic inflammation. However, AAT-deficient individuals receiving augmentation therapy had lower plasma CRP levels compared to those who are not.

Citation

Citation: Lascano J, Riley L, Khodayari N, Brantly M. Augmentation therapy modulates systemic inflammation in individuals with alpha-1 antitrypsin deficiency and chronic obstructive pulmonary disease. Chronic Obstr Pulm Dis. 2023; 10(3): 308-316. doi: http://dx.doi.org/10.15326/jcopdf.2023.0407

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Review:

Inhaled Corticosteroids and Risk of Cardiovascular Disease in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Regression

Krishna Gadhvi*1 Minnah Kandeil*1 Dinushan Raveendran*1 Jeewoo Choi*1 Nia Davies, BSc1 Sukanya Nanchahal, BSc1 Oliva Wing, BSc1 Jennifer Quint, PhD, MSc2 Hannah Whittaker, PhD, MSc2

Author Affiliations

  1. Faculty of Medicine, Imperial College London, London, United Kingdom
  2. School of Public Health and the National Heart and Lung Institute, Imperial College London, London, United Kingdom
*joint first authors

Address correspondence to:

Hannah Whittaker, PhD, MSc
Floor 9
Sir Michael Uren Building
86 Wood Lane W12 0BZ
London, United Kingdom
Email: h.whittaker@imperial.ac.uk

Abstract

Background: Previous studies have reported mixed associations between inhaled corticosteroids (ICSs) and cardiovascular disease (CVD) in people with chronic obstructive pulmonary disease (COPD). Using updated literature, we investigated the association between ICS-containing medications and CVD in COPD patients, stratified by study-related factors.

Methods: We searched MEDLINE and EMBASE for studies that reported effect estimates for the association between ICS-containing medications and the risk of CVD in COPD patients. CVD outcomes specifically included heart failure, myocardial infarction, and stroke-related events. We conducted a random-effects meta-analysis and a meta-regression to identify effect-modifying study-related factors.

Results: Fifteen studies met inclusion criteria and investigated the association between ICS-containing medications and the risk of CVD. Pooled results from our meta-analysis showed a significant association between ICS-containing medication and reduced risk of CVD (hazard ratio 0.87, 95% confidence intervals 0.78 to 0.97). Study follow-up time, non-ICS comparator, and exclusion of patients with previous CVD modified the association between ICS use and risk of CVD.

Conclusions: Overall, we found an association between ICS-containing medications and reduced risk of CVD in COPD patients. Results from the meta-regression suggest that subgroups of COPD patients may benefit from ICS use more than others and further work is needed to determine this.

Citation

Citation: Gadhvi K, Kandeil M, Raveendran D, et al. Inhaled corticosteroids and risk of cardiovascular disease in chronic obstructive pulmonary disease: a systematic review and meta-regression. Chronic Obstr Pulm Dis. 2023; 10(3): 317-327. doi: http://dx.doi.org/10.15326/jcopdf.2022.0386

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Brief Report:

Decreased Cardiac Autonomic Function is Associated with Higher Exacerbation Risk and Symptom Burden in Chronic Obstructive Pulmonary Disease

Sarath Raju, MD, MPH1 Han Woo, PhD1 Ashraf Fawzy, MD, MPH1 Nirupama Putcha, MD, MHS1 Aparna Balasubramanian, MD, MHS1 Stephen C. Mathai1 Ronald D. Berger, MD, PhD1 Nadia N. Hansel, MD, MPH1,2 Meredith C. McCormack, MD, MHS1,2

Author Affiliations

  1. Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
  2. Department of Environmental Health Sciences and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland

Address correspondence to:

Sarath Raju MD, MPH
Division of Pulmonary and Critical Care Medicine
Johns Hopkins University
5501 Hopkins Bayview Circle 4th Floor
Baltimore, MD, 21224
Phone: (410) 550-2511
Email: sraju3@jhmi.edu

Abstract

Current measures of chronic obstructive pulmonary disease (COPD) severity, including lung function, do not fully explain symptom burden, and there is a need to identify predictors of exacerbation risk and morbidity. Autonomic dysfunction may be implicated in both cardiovascular and respiratory morbidity in COPD and convey risk for exacerbations. Heart rate variability (HRV) is a marker of cardiac autonomic function that is predictive of cardiovascular health and has promise as a non-invasive COPD biomarker. The CLEAN AIR Heart study provided an opportunity to investigate the association between HRV and COPD morbidity among former smokers with moderate-severe COPD. Eighty-five participants, contributing 305 HRV measurements, underwent repeated clinical assessments over 4 study periods that included a 24-Holter monitoring assessment of HRV. HRV measures of interest were standard deviation of normal-to-normal intervals, (SDNN) (overall HRV) and root-mean-square of successive differences (RMSSD) (parasympathetic function). Exacerbation risk was assessed using negative binomial models, and mixed-effects models analyzed associations between HRV and symptoms. Decreases in SDNN (incidence rate ratio [IRR]1.40; 95% confidence interval [CI] 1.13 to1.74) and RMSSD (IRR 1.60; 95% CI 1.07 to 2.37) were associated with severe exacerbation risk. Decreases in SDNN were associated with higher St George’s Respiratory Questionnaire scores, COPD Assessment Test scores, and chronic bronchitis symptoms. Findings demonstrate that HRV is associated with COPD symptom burden and exacerbation risk. HRV may represent an important biomarker with the potential to identify high-risk COPD populations.

Citation

Citation: Raju S, Woo H, Fawzy A, et al. Decreased cardiac autonomic function is associated with higher exacerbation risk and symptom burden in chronic obstructive pulmonary disease. Chronic Obstr Pulm Dis. 2023; 10(3): 328-334. doi: http://dx.doi.org/10.15326/jcopdf.2023.0410

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