copd | Journal of the COPD Foundation

Kelly Chen, MS^1* Mostafa Aglan, MD^1* Alexandra Purcell² Lina Nurhussien, MPH^1* Petros Koutrakis, PhD³ Brent A. Coull, PhD⁴ Andrew Synn, MD¹ Mary B. Rice, MD, MPH¹

Abstract

Rationale: Although physical activity is strongly encouraged for patients with chronic obstructive pulmonary disease (COPD), it is unknown if physical activity affects daily exposure to air pollution, or whether it attenuates or exacerbates the effects of pollution on the airways among adults with COPD.

Methods: Thirty former smokers with moderate-to-severe COPD in Boston were followed for 4 non-consecutive months in different seasons. We assessed daily lung function (forced expiratory volume in 1 second [FEV₁] and forced vital capacity [FVC]), prior-day personal pollutant exposure measured by portable air quality monitors (fine particulate matter [PM_2.5] nitrogen oxide [NO₂], and ozone [O₃]), and daily step count. We constructed multi-level linear mixed-effects models with random intercepts for person and person-observation month, adjusting for demographic/seasonal covariates to test if step count was associated with daily pollution exposure, and if associations between prior-day pollution and lung function differed based on prior-day step count. Where effect modification was found, we performed stratified analyses by tertile of step count.

Results: Higher daily step count was associated with higher same-day personal exposure to PM_2.5, and O₃ but not NO₂. Each interquartile range (IQR) increment in step count was associated with 0.97 µg/m³ (95%CI: 0.30, 1.64) higher exposure to PM_2.5and 0.15 parts per billion (95% CI: -0.05, 0.35) higher exposure to O₃ in adjusted models. We observed an interaction between prior-day NO₂ and step count on FEV₁ and FVC (P_interaction<0.05) in which the negative associations between NO₂ and lung function were reduced or absent at higher levels of daily activity. For example, FEV₁was 28.5 mL (95%CI: -41.0, -15.9) lower per IQR of NO₂ in the lowest tertile of step count, but there was no association in the highest tertile of step count (-1.6mL, 95% CI: -18.4, 15.2).

Conclusions: Higher physical activity was associated with modestly higher daily exposure to PM_2.5and O₃ and may attenuate the association between NO₂ exposure and lung function.

The Association Between Systemic Arterial Hypertension and Chronic Obstructive Pulmonary Disease. Results from the U.S. National Health and Nutrition Examination Survey 1999-2018: A Cross-sectional Study

Xiaopeng Liang, MD¹ Oscar Hou In Chou, MSc¹ Bernard MY Cheung, PhD^1,2,3

Development of a Communication Instrument to Address Sexuality in COPD: COSY

Claudia Steurer-Stey, MD^1,2 Kaba Dalla Lana, BSc¹ Alexandra Strassmann, PhD, MAS, MS¹ Stefanie Gonin-Spahni, DrPhil³ Michelle Borgmann, MSc³ Ursina Brun del Re, DrPhil⁴ Sebastian Haas, MD⁵ Eliane Sarasin, MD⁶ Andrea Burri, PhD⁷ Anja Frei, DrPhil¹ Milo A. Puhan, MD, PhD¹

Airway and Systemic Prostaglandin E2 Association with COPD Symptoms and Macrophage Phenotype

Vickram Tejwani, MD^1,2 Andres F. Villabona-Rueda, MD² Pratik Khare, MS³ Cissy Zhang, BS⁴ Anne Le, MD^3,4,5 Nirupama Putcha, MD, MHS² Franco D’Alessio, MD² Neil E. Alexis, PhD⁶ Nadia N. Hansel, MD, MPH² Ashraf Fawzy, MD, MPH²

Physical Activity and Symptom Burden in COPD: The Canadian Obstructive Lung Disease Study

Loes Oostrik, MSc¹ Jean Bourbeau, MD, MSc^2,3,4 Dany Doiron, PhD^2,3 Bryan Ross, MD, MSc⁴ Pei Zhi-Li, MSc^2,3 Shawn D. Aaron, MD⁵ Kenneth R. Chapman, MD, MSc⁶ Paul Hernandez, MDCM⁷ François Maltais, MD⁸ Darcy D. Marciniuk, MD⁹ Denis O’Donnell, MD¹⁰ Wan C. Tan, MD¹¹ Don D. Sin, MD, MPH¹¹ Brandie Walker, MD, PhD¹² Tania Janaudis-Ferreira, PhD, MSc^2,3,13

Ambient Air Pollution Exposure and Sleep Quality in COPD

Mudiaga O. Sowho, MD, MPH¹ Abigail L. Koch, MD² Nirupama Putcha, MD, MHS¹ Han Woo, PhD¹ Amanda Gassett, MS³ Laura M. Paulin, MD, MHS⁴ Kirsten Koehler, PhD⁵ R. Graham Barr, MD⁶ Alejandro P. Comellas, MD⁷ Christopher B. Cooper, MD, PhD⁸ Igor Barjaktarevic, MD⁸ Michelle R. Zeidler, MD⁸ Martha E. Billings, MD, MS³ Russell P. Bowler, MD, MPH⁹ MeiLan K. Han, MD, MS¹⁰ Victor Kim, MD¹¹ Robert Paine III, MD¹² Trisha M. Parekh, DO, MSPH¹³ Jerry A. Krishnan, MD, PhD¹⁴ Stephen P. Peters, MD, PhD¹⁵ Prescott G. Woodruff, MD, MPH¹⁶ Aaron M. Baugh, MD¹⁶ Joel D. Kaufman, MD, MPH³ David Couper, PhD¹⁷ Nadia N. Hansel, MD, MPH¹

Author Affiliations

Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, United States
Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, United States
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States
Department of Medicine, Dartmouth-Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States
Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States
Department of Medicine, Columbia University Medical Center, New York, New York, United States
Division of Pulmonary, Critical Care, and Occupational Medicine, College of Medicine, University of Iowa, Iowa City, Iowa, United States
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California Los Angeles, Los Angeles, California, United States
Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colorado, United States
Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, United States
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, United States
Division of Respiratory, Critical Care and Occupational Medicine, University of Utah, Salt Lake City, Utah, United States
Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States
Division of Pulmonary, Critical Care, Sleep, and Allergy, University of Illinois at Chicago, Chicago, Illinois, United States
Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University, Winston-Salem, North Carolina, United States
Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Francisco, San Francisco, California, United States
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

The Influence of Provider Connectedness on Continuity of Care and Hospital Readmissions in Patients With COPD: A Claims Data-Based Social Network Study

Johanna Forstner, MSc¹ Jan Koetsenruijter, PhD¹ Christine Arnold, MSc¹ Gunter Laux, PhD¹ Michel Wensing, PhD¹

Persistent Steroid Exposure Before Coronavirus Disease 2019 Diagnosis and Risk of Hospitalization in Patients With Chronic Obstructive Pulmonary Disease

Posted in: Original Research, Covid19, Volume 10 | Issue 1

Laura C. Myers, MD, MPH^1,2 Richard K. Murray, MD³ Bonnie M.K. Donato, PhD⁴ Vincent X. Liu, MD, MSc^1,2 Patricia Kipnis, PhD^1,2 Asif Shaikh, MD, DrPH⁵ Jessica Franchino-Elder, PhD, MPH⁴

Primary Care Provider Experience With Proactive E-Consults to Improve COPD Outcomes and Access to Specialty Care

Laura J. Spece, MD, MS^1,2,3* William G. Weppner, MD, MPH^3,4* Bryan J. Weiner, PhD^5,6 Margaret Collins, PhD¹ Rosemary Adamson, MB, BS² Douglas B. Berger, MD, MLitt^2,3 Karin M. Nelson, MD, MSHS^1,2,3 Jennifer McDowell, BS¹ Eric Epler, BS¹ Paula G. Carvalho, MD^3,4 Deborah M. Woo, PharmD² Lucas M. Donovan, MD, MS^1,2,3 Laura C. Feemster, MD, MS^1,2,3 David H. Au, MD, MS^1,2,3 George Sayre, PsyD^1,5

Novel SERPINA1 Alleles Identified Through a Large Alpha-1 Antitrypsin Deficiency Screening Program and Review of Known Variants

Gayle S. Wiesemann, BS¹ Regina A. Oshins, BS² Tammy O. Flagg, MB, MT² Mark L. Brantly, MD²

Common Respiratory Pathogens Other Than Haemophilus in Small Airways Are Associated With Neutrophilic Inflammation and Poor Health Status in Stable COPD Patients

Posted in: Short Communication, Volume 10 | Issue 1

Nawaf M. Alotaibi, MD, MSc^1,2 Sheena Tam, BSc¹ Stephan F. van Eeden, MD¹ Tawimas Shaipanich, MD^3,4 Stephen Lam, MD^3,4 Janice M. Leung, MD^1,3 Don D. Sin, MD, MPH^1,3

Health Care Professionals’ Herpes Zoster Awareness and Vaccine Recommendations for Patients with COPD

Barbara P. Yawn, MD, MSc, MSPH^1,2* Natalia Y. Loskutova, MD, PhD^3* Debora D. Merrill, MBA² Sergio Martinez² Elisabeth Callen, PhD³ Janice Cotton, MA² Jennifer K. Carroll, MD, MPH^3,4 Dennis Williams, PharmD⁵

Patient-Reported Pulmonary Symptoms, Exacerbations, and Management in a Cohort of Patients With Alpha-1 Antitrypsin Deficiency

Radmila Choate, PhD, MPH¹ Robert A. Sandhaus, MD, PhD^2,3 Kristen E. Holm, PhD, MPH^2,3 David M. Mannino, MD⁴ Charlie Strange, MD^3,5

Impact of the Coronavirus Disease 2019 Pandemic on Physical and Mental Health of Patients With COPD: Results From a Longitudinal Cohort Study Conducted in the United States (2020-2021)

Posted in: Original Research, Covid19, Volume 9 | Issue 4

William Z. Zhang, MD¹* Stephanie L. LaBedz, MD²* Janet T. Holbrook, PhD³ Andrew Gangemi, MD⁴ Ramasubramanian Baalachandran, MBBS⁵ Michelle N. Eakin, PhD, MD⁶ Robert A. Wise, MD⁶ Kaharu Sumino, MD, MPH⁷ for the American Lung Association Airways Clinical Research Centers.

Varenicline for Gradual Versus Abrupt Smoking Cessation in Poorly Motivated Smokers With COPD: A Prematurely Terminated Randomized Controlled Trial

Abraham Bohadana, MD¹ Ariel Rokach, MD¹ Pascal Wild, PhD² Bela Peker¹ Yossi-Freier Dror, PhD³ Polina Babai³ Nissim Arish, MD¹ Gabriel Izbicki, MD¹

Abstract

Background: Although smoking is the leading cause of chronic obstructive pulmonary disease (COPD), many patients with COPD smoke, highlighting the need for effective smoking cessation interventions in this population. This study examined the efficacy and safety of varenicline in increasing smoking cessation rates through "gradual" versus "abrupt" cessation in COPD patients with low motivation to quit smoking.

Methods: A randomized, open label, 30-week, controlled trial (ClinicalTrials.gov identifier: NCT02894957) was conducted between January 2019 and October 2020 at a center in Israel. Smokers with COPD, poorly motivated to quit, were randomized to 6 weeks of varenicline for smoking reduction and a target quit day (TQD) at the end of week 6 (gradual cessation group) or ad libitum smoking for 5 weeks, 1 week of varenicline, and a TQD at the end of week 6 (abrupt cessation group). After the pre-quit phase, both groups received 12-week regular varenicline treatment and 12-week follow-up. Primary outcome was biochemically-validated continuous abstinence for weeks 6–30. Secondary outcomes were: (1) biochemically-confirmed7-day point prevalence abstinence for weeks 4–30, (2) efficient smoking reduction (≥50% in number of cigarettes/day) in the pre-quit phase; and (3) number of cigarettes/day, motivation to quit, and changes in respiratory symptoms and spirometry from baseline through week 30.

Results: A drug recall issued by the study sponsor stopped the study after 70/242 (28.9%) patients had been enrolled. The gradual cessation group (n=29) had significantly higher continuous abstinence rates from TQD through week 30 versus the abrupt cessation group (n=41): 20.7% versus 4.9% (odds ratio [OR]=5.09; 95% confidence interval [CI] 0.89-29.17; p=0.048) and higher 7-day point prevalence abstinence levels at all time points but week 18 (p=0.027 at week 6, 0.056 at week 7, and 0.096 at week 9). Motivation to quit increased (p=0.002) and the number of cigarettes/day decreased (p=0.002) over time in both groups. Respiratory symptoms, but not spirometry, improved in both groups at week 30. Treatment was safe and well tolerated.

Conclusions: In poorly motivated smokers with COPD, using varenicline for a 6-week gradual smoking cessation before TQD, compared with abrupt cessation, significantly increased quit rates up to 6 months. Results were not affected by the smaller-than-expected sample size. Further studies are needed to confirm these data.

The Effect of Rurality and Poverty on COPD Outcomes in New Hampshire: An Analysis of Statewide Hospital Discharge Data

Jacob S. Warner, DO¹ Jane M. Bryan² Laura M. Paulin, MD, MHS³

Abstract

Purpose: Individuals in rural areas of the United States have a greater risk of chronic obstructive pulmonary disease (COPD) and have worse COPD outcomes. New Hampshire (NH) is split between non-rural and rural counties.

Methods: We examined differences in COPD exacerbation rates ([encounters per county/county population of 35 years of age and older] × 100), length of stay (LOS), and total charges by rurality, determined by the 2013 National Center for Health Statistics rural-urban classification. Linear regression analysis determined the association of rural status on COPD outcomes, adjusting for age, gender, insurance status, and county-level smoking prevalence.

Findings: A total of 15,916 encounters were analyzed, of which 5805 were inpatient and 10,111 were from the emergency department, 7058 (44%) were male, and the mean age was 65.6. A total of 31% were from large, fringe metro counties, 25.9% were from medium metro counties, 37.6% were from micropolitan counties, and 5.5% were from non-core counties. In multivariable regression, rural counties had higher COPD exacerbation rates compared to urban counties (non-core beta=0.18, [confidence interval (CI) 0.16, 0.20]; micropolitan beta=0.02, CI [0.01, 0.03]); medium metro counties (beta=-0.07, Cl [-0.09, -0.06]) had lower rates of COPD exacerbations (P < 0.001 for all). Compared to urban counties, encounters from rural counties had lower total charges (medium metro beta=-1695 [-2410, -980]; micropolitan beta=-2701 [-3315, -2088]; non-core beta=-4453 [-5646, -3260], all p<0.001). LOS did not differ by rurality.

Conclusions: Accounting for poverty and other sociodemographic factors, the rates of COPD exacerbation encounters were higher in rural versus non-rural NH counties. Additionally, non-rural areas carried higher total charges, potentially due to more resource availability. These results support the need for future interventions to improve outcomes in rural COPD patients.

Antibody Response to Severe Acute Respiratory Syndrome Coronavirus-2 Vaccination in COPD: A Cohort Study

Posted in: Short Communication, Covid19, Volume 9 | Issue 4

Éliane Pelletier, MD^1,2 Philippe Desmeules, PhD³ Yves Lacasse, MD, MSc^1,2 Sophie Tanguay, BSc^1,2 Julie Milot, MD, PhD^1,2 Mathieu C. Morissette, PhD^1,2 François Maltais, MD^1,2

Journal Club: Impaired Ventilatory Efficiency and Exercise Intolerance in Former/Current Smokers With Dyspnea Disproportionate to Their Lung Function: Pathophysiological Insights Gained Through Cardiopulmonary Exercise Testing

Posted in: Journal Club, Volume 9 | Issue 3

Ron Balkissoon, MD, MSc¹ Takudzwa Mkorombindo, MD²

Predictors of High Sputum Eosinophils in COPD

Xiang Wen, MD^1* Jieqi Peng, MD^1* Youlan Zheng, MD^1* Jiaxing Liu, MD¹ Heshen Tian, MD, PhD¹ Fan Wu, MD¹ Zihui Wang, MD¹ Huajing Yang, MD¹ Zhishan Deng, MD¹ Shan Xiao, MD¹ Peiyu Huang, MD¹ Jianwu Xu, MD¹ Cuiqiong Dai, MD¹ Ningning Zhao, MD¹ Lifei Lu, MD¹ Jianwei Dai, PhD² Bing Li, PhD² Pixin Ran, MD, PhD^1,3 Yumin Zhou, MD, PhD^1,3

Chronic Obstructive Pulmonary Disease and Lung Cancer: A Review for Clinicians

Posted in: Review, Volume 9 | Issue 3

Gerard J. Criner, MD¹ Alvar Agusti, MD² Hossein Borghaei, DO³ Joseph Friedberg, MD¹ Fernando J. Martinez, MD ⁴ Curtis Miyamoto, MD⁵ Claus F. Vogelmeier, MD⁶ Bartolome R. Celli, MD^7,8

Patterns and Predictors of Air Cleaner Adherence Among Adults with COPD

Wendy Lorizio, MD, MPH¹ Han Woo, PhD¹ Meredith C. McCormack, MD, MHS¹ Chen Liu, MHS¹ Nirupama Putcha, MD, MHS¹ Megan Wood, MS² Timothy Green, BS² Parisa Kaviany, MD³ Daniel Belz, MD, MPH¹ Ashraf Fawzy, MD, MPH¹ Sara Carson, MD, MHS¹ Michelle N. Eakin, PhD, MA¹ Kirsten Koehler, PhD² Nadia N. Hansel, MD, MPH^1,2

Machine Learning Prediction of Progression in Forced Expiratory Volume in 1 Second in the COPDGene^® Study

Adel Boueiz, MD, MMSc^1,2* Zhonghui Xu, MS^1* Yale Chang, PhD³ Aria Masoomi, PhD³ Andrew Gregory, BS¹ Sharon M. Lutz, PhD⁴ Dandi Qiao, PhD¹ James D. Crapo, MD⁵ Jennifer G. Dy, PhD³ Edwin K. Silverman, MD, PhD^1,2 Peter J. Castaldi, PhD^1,6 for the COPDGene Investigators

Giving Voice to People – Experiences During Mild to Moderate Acute Exacerbations of COPD

Ana Machado, PT, MSc^1,2,3,4 Sara Almeida, GT, MSc, PhD^1,5 Chris Burtin, PT, MSc, PhD^3,4 Alda Marques, PT, MSc, PhD^1,5

Short-Term Impact of the Frequency of COPD Exacerbations on Quality of Life

Erin R. Camac, DO¹ Natalie A. Stumpf, BA² Helen K. Voelker, BS³ Gerard J. Criner, MD²; for the COPD Clinical Research Network

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

Posted in: Journal Club, Volume 9 | Issue 2

Takudzwa Mkorombindo, MD¹ Ron Balkissoon, MD²

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

Posted in: Short Communication, Volume 9 | Issue 2

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

Abstract

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

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

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

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

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

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

Posted in: Letters to the Editor, Volume 9 | Issue 2

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

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

Posted in: Original Research, Volume 9 | Issue 2

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

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

Posted in: Review, Volume 9 | Issue 2

Janine Dretzke, MSc¹ Jingya Wang, PhD¹ Mi Yao, MSc¹ Naijie Guan, MSc¹ Myra Ling² Erica Zhang² Deyashini Mukherjee, MBBS³ James Hall, PhD⁴ Sue Jowett, PhD⁴ Rahul Mukherjee, MBBS, FRCP⁵ David J. Moore, PhD¹ Alice M. Turner, MBChB, PhD^1,5

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

Posted in: Original Research, Volume 9 | Issue 2

Jiaqiang Zhang, MD, PhD^1* Wei-Chun Lin, MD^2* Kuo-Chin Chiu, MD³ Szu-Yuan Wu, MD, MPH, PhD^4,5,6,7,8,9
^*These authors have contributed equally to this study (coauthors).

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

Posted in: Perspectives, Volume 9 | Issue 2

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

Feasibility of Using Daily Home High-Flow Nasal Therapy in COPD Patients Following a Recent COPD Hospitalization

Posted in: Original Research, Volume 9 | Issue 1

Gerard J. Criner, MD¹ Lii-Yoong H. Criner, RN, CRN¹ Sheril A. George, BS, RRT¹ Jiji K. Thomas, MBBS¹ Michael R. Jacobs, PharmD¹

Exploring the Patient Experience with Noninvasive Ventilation: A Human-Centered Design Analysis to Inform Planning for Better Tolerance

Posted in: Original Research, Volume 9 | Issue 1

Jill L. McCormick, MBA¹ Taylar A. Clark, BA² Christopher M. Shea, PhD³ Dean R. Hess, RRT, FAARC, PhD^4,5 Peter K. Lindenauer, MD, MSc^2,6,7 Nicholas S. Hill, MD⁸ Crystal E. Allen, RN¹ MaryJo S. Farmer, MD, PhD^6,9 Ashley M. Hughes, PhD¹⁰ Jay S. Steingrub, MD^6,9 Mihaela S. Stefan, MD, PhD^2,6

Designing Clinical Trials in “Regular” COPD Versus Alpha-1 Antitrypsin Deficiency-Associated COPD: “More Alike Than Unalike?”

Posted in: Perspectives, Volume 9 | Issue 1

James K. Stoller, MD, MS¹

Abstract

Alpha-1 antitrypsin deficiency (AATD) predisposes to emphysema, liver disease, and panniculitis. This emphysema risk naturally invites a comparison between “regular” chronic obstructive pulmonary disease (COPD) (i.e., unrelated to AATD) and AATD-associated emphysema.

Several features characterize both conditions. Both can be life-limiting and highly debilitating. Both are highly under-recognized.

An important corollary of this comparison between “regular” COPD and AATD-associated COPD is whether both should be treated similarly and whether clinical trials to assess new therapies can be conducted similarly in both. Here, the distinctions between “regular” COPD and AATD-associated COPD are quite pronounced. Therapeutically, sparse available data suggest that lung volume reduction surgery confers less improvement in forced expiratory volume in 1 second (FEV₁) in AATD and that such benefits are shorter-lived. Perhaps the most striking contrast between the 2 conditions is that clinical trial designs and conduct are necessarily very different. The relative scarcity of diagnosed individuals with AATD hampers recruitment to trials. Furthermore, primary outcome measures in trials of “regular” COPD must differ markedly from those of AATD-associated emphysema. Specifically, power calculations show that FEV₁ and exacerbation frequency, which are amply represented as endpoints in large COPD trials, are infeasible in studies of AATD-associated emphysema. Rather, in the 3 available randomized controlled trials of intravenous augmentation therapy, the rate of emphysema progression based on serial computed tomography densitometry measurements has been the only feasible primary outcome measure.

These considerations underscore the distinctive challenges and needs of conducting treatment trials in AATD-associated emphysema and emphasize that, with regard to clinical study design, the 2 conditions are “more unalike than alike.”

Journal Club: Non-invasive Mechanical Ventilation in Stable COPD

Posted in: Journal Club, Volume8 | Issue 4

Takudzwa Mkorombindo, MD¹ Ron Balkissoon, MD²

Self-reported COPD Medication Use and Adherence in the COPD Foundation Patient- Powered Research Network

Cara B. Pasquale, MPH¹ Radmila Choate, PhD, MPH^1,2 Gretchen McCreary, MA¹ Richard A. Mularski, MD, MSHS, MCR^3,4,5 William Clark, BS¹ MaryEllen Houlihan¹ Elisha Malanga, BS¹Barbara P. Yawn, MD, MSc, MSPH^1,6

Increased Health Care Resource Utilization and Costs Associated with Herpes Zoster Among Patients Aged ≥50 Years with Chronic Obstructive Pulmonary Disease in the United States

Parinaz Ghaswalla, PhD^1* Philippe Thompson-Leduc, MSc² Wendy Y. Cheng, PhD, MPH³ Colin Kunzweiler, PhD, MS³ Min-Jung Wang, ScD³ Michael Bogart, PharmD⁴ Brandon J. Patterson, PharmD, PhD^1** Mei Sheng Duh, ScD, MPH³ John Wojciehowski, BA³ Suna Park, MSc³ Barbara P. Yawn, MD, MSc⁵

Outcomes of Patients with COPD Hospitalized for Coronavirus Disease 2019

Daniel A. Puebla Neira, MD¹ Abigail Watts, MD ¹ Justin Seashore, MD¹ Alexander Duarte, MD¹ Shawn P. Nishi, MD¹ Efstathia Polychronopoulou, MS, MPH² Yong-Fang Kuo, PhD^2-3 Jacques Baillargeon, PhD³ Gulshan Sharma, MD, MPH^1,3

Decrease in Exacerbations During the Coronavirus Disease 2019 Pandemic in a Cohort of Veterans with COPD

Posted in: Short Communication, Volume8 | Issue 4

Christian Trujillo, MD¹ Brian Garnet, MD^2,3 Ali Vaeli Zadeh, MD² Gisel Urdaneta, MD² Michael Campos, MD^2,3

Cytomegalovirus Seropositivity is Associated with Airflow Limitation in a Cohort of Veterans with a High Prevalence of Smoking

Robert Burkes, MD, MSCR^1,2 Andrew Osterburg, PhD¹ Timothy Hwalek, DO¹ Laura Lach, RRT² Ralph J. Panos, MD^1,2 Michael T. Borchers, PhD^1,2

Losartan Effects on Emphysema Progression Randomized Clinical Trial: Rationale, Design, Recruitment, and Retention