Chronic Obstructive Pulmonary Diseases:Journal of the COPD Foundation

Volume 8, Issue 4 - 2021 | Plain Language Summaries

Short summaries, in non-technical, simple language of articles published in the most recent issue of Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation are provided here. Links to the full, published research article are provided with each summary. The Journal is indexed by PubMed, PubMed Central, Scopus and Web of Science.

All summaries for the current issue are listed below in the order of publication, scroll down.

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

American Lung Association Airways Clinical Research Centers*
*Writing Committee: Robert A. Wise, MD; Janet T. Holbrook, PhD; Robert H. Brown, MD; Gerard J. Criner, MD; Mark T. Dransfield, MD; MeiLan K. Han, MD, MPH; Jerry A. Krishnan, MD, PhD; Ellen Looney, MBA; Enid Neptune, MD; Vicky Palombizio, BA; Alexis Rea, MPH

Losartan is a generic drug used to treat high blood pressure; it works by promoting relaxation of blood vessels. There is evidence that losartan also affects lung tissue. Results from animal and clinical studies suggested that losartan could slow the progression of emphysema. Because losartan is a generic drug that is widely available, there are few incentives for pharmaceutical companies to evaluate other possible uses of losartan.

To test whether losartan affects emphysema, the Pulmonary Trials Cooperative consortium, which is funded by the National Institutes of Health in collaboration with the American Lung Association (ALA), funded the “Losartan Effects on Emphysema Progression (LEEP)” trial (NCT00720226).

The clinical trial enrolled 220 individuals with COPD-related emphysema at 26 clinical sites that are part of the ALA Airways Clinical Research Centers. Participants were randomly assigned to receive losartan or a matching placebo.

This paper describes the design of the trial and challenges for recruitment and follow-up of the 220 participants. The trial was completed in March 2021. The data collected from the trial are being analyzed and the results will be published in a separate publication.

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

Robert Burkes, MD, MSCR; Andrew Osterburg, PhD; Timothy Hwalek, DO; Laura Lach, RTT; Ralph J. Panos, MD; Michael T. Borchers, PhD

Cytomegalovirus (CMV) is a common viral infection that is usually not associated with a severe illness but can remain in human lung tissue once acquired and become a chronic infection. It is believed that having a virus chronically stressing the immune system leads to poor results in diseases of the lungs, including COPD. Our study describes how individuals with chronic CMV infection who smoke are more likely to have airflow obstruction than those who do not have a chronic CMV infection. We did not find a relationship with chronic CMV infection and past COPD exacerbations.

Comparative Effectiveness of Roflumilast and Azithromycin for the Treatment of Chronic Obstructive Pulmonary Disease

Jenny Lam, MD, PhD; Ivy Tonnu-Mihara, PharmD; Nicholas J. Kenyon, MD, MAS; Brooks T. Kuhn, MD, MAS

For patients who suffer frequent exacerbations from chronic obstructive pulmonary disease (COPD), roflumilast and chronic azithromycin are recommended treatments. Roflumilast is recommended for COPD patients with severe obstruction and chronic bronchitis, and chronic azithromycin has broader uses. It is unclear how these treatments compare to each other in effectiveness at reducing exacerbations which often lead to hospitalizations. We analyzed data from the Veterans Health Administration database to compare how effective roflumilast and azithromycin each are in reducing hospitalizations and deaths. We found that the patients who are prescribed roflumilast were associated with higher rates for death, COPD-related hospitalizations, and hospitalizations for all reasons. Future clinical trials are needed to directly compare the “relative efficacy” of these therapies, i.e., how well each of these drugs does, in comparison to each other, at improving outcomes.

IntraIndividual Variability in Serum Alpha-1 Antitrypsin Levels

Annie Haillot, MD; Andrée-Anne Pelland, MD; Yohan Bossé, PhD; Tomás P. Carroll, PhD; François Maltais, MD; Ronald J. Dandurand, MD

Alpha-1 antitrypsin (AAT) deficiency is the most common cause of hereditary chronic obstructive pulmonary disease (COPD). Making the diagnosis of AAT deficiency is important because there are specific treatment recommendations for this condition. When looking for AAT deficiency, measuring the level of AAT in the blood is often the first step. The level of AAT in the blood can vary and it may rise during inflammation or infection. However, little information is available regarding how much the AAT blood levels can vary when the measurement is made twice, but at different times, in the same individual. The purpose of our study was to evaluate how often the AAT levels in people with COPD are the same, when measured at different times. We evaluated 255 people with COPD who had their AAT serum levels measured twice. We found that AAT levels in an individual has low reproducibility—meaning an individual’s levels are rarely the same, when tested. This is especially true for individuals with intermediate AAT deficiency. This high variability was not explained by the patients’ individual characteristics. These findings suggest that caution is needed before confirming or excluding a diagnosis of AAT deficiency solely on the basis of AAT serum levels. Genetic tests are available and should be considered to formally establish the diagnosis of AAT deficiency.

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

Cara B. Pasquale, MPH; Radmila Choate, PhD, MPH; Gretchen McCreary; MA Richard A. Mularski, MD, MSHS, MCR; William Clark, BS; MaryEllen Houlihan; Elisha Malanga, BS; Barbara P. Yawn, MD, MSc, MSPH

Inhaled medicines are important in treating chronic obstructive pulmonary disease (COPD). Studies of COPD medicines often use data from health care sources without including patients’ reports of medicine use and barriers. This study collected information from patient members of the COPD Foundations’ Patient-Powered Research Network asking about COPD medicine use, education, cost concerns, and COPD symptoms and flares. Inhaler pictures were used to improve ease of medicine reporting. Among 804 respondents, the average age was 68 years, over half (60%) were women, almost three-quarters (70%) had high levels of COPD symptoms with COPD Assessment Test scores higher than 15, and slightly half (50%) reported 2 or more flares or exacerbations in the past 12 months. Almost everyone (98%) used 1 or more inhaled medicines, and almost three-quarters (73%) used both bronchodilators and inhaled corticosteroids, and 53% used triple therapy. While most (70%) reported they were shown how to use one of their inhalers, only slightly over one-third (38%) were shown how to use all or had inhaler use observed to ensure it was correct. Respondents reported high medicine use (80.1%), but many (41%) reported trouble paying for medicines, with almost 3 out of every 10 (28%) reporting missing medications due to cost.

Pilot Study of a Patient Experience with an ELLIPTA Inhaler Electronic Medication Monitor and Associated Integrated System: A Prospective Observational Study Using the COPD Patient-Powered Research Network

Barbara P. Yawn, MD, MSc; Gretchen M. McCreary, MA; John A. Linnell, BA; Cara B. Pasquale, MPH; Elisha Malanga, BS; Radmila Choate, PhD, MPH; David A. Stempel, MD; Rahul Gondalia, PhD, MPH; Leanne Kaye, PhD, MPH; Kathryn A. Collison, MPH, PMP; Benjamin S. Wu, PharmD, MS

Some people with chronic obstructive pulmonary disease (COPD) forget or don’t use their daily inhalers. Electronic sensors can fit onto inhalers and link to an app to track inhaler use and provide reminders and education on COPD. This study asked participants to use a sensor and app with their dry powder ELLIPTA inhalers.

A total of 122 people with COPD joined the study and were sent the sensor with instructions for installation and use of the sensor and app. We studied how many days participants opened the app, how often they used their daily ELLIPTA inhaler, and what they thought about the sensor and app. A subgroup (51 people) also used sensors to monitor rescue inhalers.

Overall, the app was opened about 6 in 10 days the first month, falling to about 4 in 10 days by the third month. Participants took about 8 in 10 prescribed ELLIPTA inhaler-delivered doses over the study period whether or not they opened the app. For 51 people, rescue inhalers were used on fewer days as the study progressed.

Most participants reported high confidence in using the sensor and app and liked the reminders. This sensor and app may help with COPD self-management.

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; Philippe Thompson-Leduc, MSc; Wendy Y. Cheng, PhD, MPH; Colin Kunzweiler, PhD, MS; Min-Jung Wang, ScD; Michael Bogart, PharmD; Brandon J. Patterson, PharmD, PhD; Mei Sheng Duh, ScD, MPH; John Wojciehowski, BA; Suna Park, MSc; Barbara P. Yawn, MD, MSc

Shingles is a painful skin rash caused by the varicella zoster virus, the same virus that causes chickenpox. Individuals with chronic obstructive pulmonary disease (COPD) may be at increased risk of developing shingles. Little is known about the effect of a shingles episode on the use of medical services and costs among these individuals.

Using data from United States health insurance claims, this study found that the use of medical services among individuals aged ≥50 years with COPD, who had a shingles episode, was on average 17% higher than among those who did not have shingles.

Among individuals with COPD, total health care costs per person were $3,756 higher during the first year after shingles began compared to those who did not have shingles. Most of this cost difference (79.4%) occurred in the first month after a shingles diagnosis. These results could help to estimate the potential cost benefits of vaccination against shingles among people with COPD.

Outcomes of Patients with COPD Hospitalized for Coronavirus Disease 2019

Daniel A. Puebla Neira, MD; Abigail Watts, MD; Justin Seashore, MD; Alexander Duarte, MD; Shawn P. Nishi, MD; Efstathia Polychronopoulou, MS, MPH; Yong-Fang Kuo, PhD; Jacques Baillargeon, PhD; Gulshan Sharma, MD, MPH

Millions of people in the United States and around the world have chronic obstructive pulmonary disease (COPD). During the coronavirus disease 2019 (COVID-19) pandemic there has been controversy regarding the link between COPD and COVID-19, with some clinical investigators reporting worse outcomes in patients with COPD and COVID-19, while other investigators have reported no association.

To address this discrepancy, we performed a large, nationally representative, retrospective cohort study to evaluate whether a history of COPD was independently associated with an increased risk of death in patients hospitalized with COVID-19. We found that a diagnosis of COPD was an independent risk factor for death in adults aged 40 to 79 years of age. Patients with a personal history of COPD without allergies or other conditions that might lead to negative reactions, should receive the COVID vaccine to minimize their risk.

Objectively Measured Physical Activity in Patients with COPD: Recommendations from an International Task Force on Physical Activity

Heleen Demeyer, PT, PhD; Divya Mohan, MD, PhD; Chris Burtin, PT, PhD; Anouk W. Vaes, PhD; Matthew Heasley, M Eng; Russell P. Bowler, MD, PhD; Richard Casaburi, MD, PhD; Christopher B. Cooper, MD, PhD; Solange Corriol-Rohou, MD, PhD; Anja Frei, PhD; Alan Hamilton, PhD; Nicholas S. Hopkinson, MD, PhD; Niklas Karlsson, PhD; William D-C. Man, MD, PhD; Marilyn L. Moy, MD, PhD; Fabio Pitta, PhD; Michael I. Polkey, MD, PhD; Milo Puhan, MD, PhD; Stephen I. Rennard, MD; Carolyn L. Rochester, MD, PhD; Harry B. Rossiter, PhD; Frank Sciurba, MD; Sally Singh, PT, PhD; Ruth Tal-Singer, PhD; Ioannis Vogiatzis, PhD; Henrik Watz, MD, PhD; Rob Van Lummel, PhD; Jeremy Wyatt, MBA; Debora D. Merrill, MBA; Martijn A. Spruit, PT, PhD; Judith Garcia-Aymerich, MD, PhD; Thierry Troosters, PT, PhD; for the Chronic Lung Disease Biomarker and Clinical Outcome Assessment Qualification Consortium Task Force on Physical Activity

Physical activity is of key importance for health among healthy persons and individuals with COPD. Physical activity can be measured objectively using activity monitors. However, because several different ways are currently being used to calculate physical activity in individuals with COPD, it is difficult to make comparisons between studies. The present paper aims to provide a summary of the available literature providing explanations and reasons why objectively measured physical activity should be used in studies and as a measure of health. Our article summarizes the best practices in physical activity monitoring. It provides information on data collection (e.g., how long should the monitor be worn) and processing of data (e.g., what is the definition of a valid day). It offers researchers a guide and standards for how to consistently measure physical activity that will ultimately allow for better comparisons of study results. The present international task force, which authored this article, recommends implementing a “standard operating procedure” for gathering physical activity data and reporting in the future. This should help clarify the relationship between physical activity and clinical outcomes such as changes in health or quality of life. This “standard operating procedure” should also help measure how different treatments affect physical activity in individuals with COPD and to successfully propose a physical activity measurement that may be ultimately approved for use in clinical trials.

Use of the Evaluating Respiratory Symptoms™ in COPD as an Outcome Measure in Clinical Trials: A Rapid Systematic Review

Donald M. Bushnell, MA; Rozanne Wilson, PhD; Florian S. Gutzwiller, MD, MPH; Nancy K. Leidy, PhD Carolina Hache, PhD; Chau Thach; Claus F. Vogelmeier, MD

The Evaluating Respiratory Symptoms™ in Chronic Obstructive Pulmonary Disease (E-RS™: COPD) is a patient-reported tool that was created to measure the severity of respiratory symptoms and test the effects of treatment in individuals with stable COPD. It has been approved by the U.S. Food and Drug Administration and the European Medicines Agency for use in clinical trials.

There is limited knowledge of how the E-RS: COPD has been used in clinical trials and how the E-RS: COPD has performed as a symptoms measuring tool since it was first approved for use. This review study found that several clinical trials have successfully used this patient-reported tool as an endpoint to determine whether a treatment had the desired positive effect on symptoms. The review study’s findings also showed that the E-RS: COPD is a responsive measure that corresponds well with other relevant outcome measures.

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

Christian Trujillo, MD; Brian Garnet, MD; Ali Vaeli Zadeh, MD; Gisel Urdaneta, MD; Michael Campos, MD

This study followed a group of 123 veterans with COPD from 2017 until December 2020 to determine how often they had exacerbations before and during the coronavirus disease 2019 (COVID-19) pandemic. Phone interviews were performed in 2020 to inquire about adherence to recommended COVID-19 preventative measures, such as social distancing and regular mask use.

The study found a significant decrease in COPD exacerbations during the COVID-19 pandemic compared to the previous 3 years (21% versus 36%-42%). We also found high compliance rates with preventative measures against COVID-19 but noticed that patients who felt better and had better lung function tended to follow the preventative measures less.

This significant decrease in COPD exacerbations during the COVID-19 pandemic may be due to patients following preventative measures against viral infection. Implementing some of these measures, such as mask use and frequent hand washing, may be beneficial to prevent exacerbations in a post-pandemic era.