Chronic Obstructive Pulmonary Diseases:Journal of the COPD Foundation

Volume 10, Issue 1 - 2023 | 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.

Association of Hoover’s Sign with Maximal Expiratory-to-Inspiratory Pressure Ratio in Patients with COPD

Thomas G. Maloney, DO; Zachary S. Anderson, DO; Ashley B. Vincent, DO; Adam L. Magiera, DO; Philip C. Slocum, DO

Some patients with COPD develop an abnormal rib motion, named Hoover’s sign, in which the bottom ribs move inward rather than outward when inhaling. This abnormal motion is the result of abnormal function of the diaphragm—the major muscle involved in breathing. A previous study showed that diaphragm paralysis can be predicted by specific values on a breathing test (specifically, a test that measures respiratory pressures). We sought to determine whether patients with advanced COPD, who had Hoover’s sign, had differences on this breathing test compared to patients with advanced COPD without Hoover’s sign. When comparing those with and without Hoover’s sign, we also wanted to know if patient characteristics and specific pulmonary function test variables differed between the 2 groups.

Patients with advanced COPD were examined by 2 resident physicians trained in detecting Hoover’s sign. There was strong agreement in the exam findings between the observers. We found that the breathing test variable was higher in patients with COPD and Hoover’s sign. This finding suggests the breathing test can predict abnormal functioning of the diaphragm and Hoover’s sign in patients with advanced COPD.

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

Gayle S. Wiesemann, BS; Regina A. Oshins, BS; Tammy O. Flagg, MB, MT; Mark L. Brantly, MD

Alpha-1-antitrypsin deficiency is an inherited cause of COPD and liver disease affecting up to 1 in 2000-4000 individuals in North America and Europe. The most common gene mutation that causes the disease is called Z alpha-1-antitrypsin. This mutation causes the protein that the alpha-1-antitrypsin gene produces to mis-form in the cell. This then prevents the protein from being released, resulting in a lack of the protein in the body. While most individuals with alpha-1-antitrypsin deficiency have the Z mutation, there are a number of very rare mutations of the alpha-1-antitrypsin gene that can also cause the disease. These rare mutations are very important in helping scientists understand how proteins created by certain gene mutations fail to leave the cell and may allow for the development of new therapies to treat alpha-1-antitrypsin deficiency. In this study the authors identified a number of these mutations and compared them to other rare mutations previously identified.

Urine and Plasma Markers of Platelet Activation and Respiratory Symptoms in COPD

Ashraf Fawzy, MD, MPH; Nirupama Putcha, MD, MHS; Sarath Raju, MD, MPH; Han Woo, PhD; Cheng Ting Lin, MD; Robert H. Brown, MD, MPH; Marlene S. Williams, MD; Nauder Faraday, MD, MPH; Meredith C. McCormack, MD, MHS; Nadia N. Hansel, MD, MPH

Prior studies have shown that in COPD, fewer flares or exacerbations and reduced respiratory symptoms were associated with the use of aspirin. Aspirin blocks the activity of platelets, which are small cell fragments known for their role in clotting, but which are also involved in inflammation and problems with the immune system. While it is known that platelet activity is higher among individuals with COPD, it is unknown whether activated platelets play a role in respiratory symptoms.

In this study, three markers of platelet activation –one in urine (11-dehydro-thromboxane B2) and two in blood (CD40L and P-selectin) –were measured multiple times over a 6 to 9-month period in 169 former smokers with moderate-severe COPD. Higher levels of the urinary marker were associated with worse respiratory symptoms, worse health status, and worse quality of life, whereas the blood markers were not associated with COPD outcomes. The urinary marker was associated with COPD outcomes regardless of the presence of cardiovascular disease or the use of platelet-blocking medications like aspirin.

The findings of this study add to information from previous studies that have suggested that activated platelets have a role in COPD and could be targeted with medications. Future studies investigating more specific markers of platelet activation are needed.

Mortality Risk and Serious Cardiopulmonary Events in Moderate-to-Severe COPD: Post Hoc Analysis of the IMPACT Trial

J. Michael Wells, MD; Gerard J. Criner, MD; David M.G. Halpin, MD; MeiLan K. Han, MD; Renu Jain, PhD; Peter Lange, MD; David A. Lipson, MD; Fernando J. Martinez, MD; 1 Dawn Midwinter, MSc; Dave Singh, MD; Robert A. Wise, MD

Exacerbations or “flare-ups” of chronic obstructive pulmonary disease (COPD) are associated with negative cardiac (heart) events, and an increased risk of dying. The IMPACT study included patients with COPD and a history of exacerbations in the past year. We examined the relationship between severe cardiopulmonary (heart and lung) events, including severe exacerbations and pneumonia requiring hospitalization, and death among patients from the IMPACT study.

We found that 49% of patients suffered a moderate/severe exacerbation during the study period. During a severe exacerbation event, patients had a 41-times higher risk of dying than they did during the non-exacerbating state prior to the severe exacerbation event.

Fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI), a single-inhaler triple therapy, reduced the risk of severe cardiopulmonary events by 16.5% and by 6.2% compared with UMEC/VI and FF/VI dual therapies, respectively. Although patients receiving FF, an inhaled corticosteroid, were more likely to have a pneumonia event, the reduced risk of severe exacerbations and death seen overall suggests that the addition of an inhaled corticosteroid to dual bronchodilator therapy could benefit patients with COPD.

Our results confirm substantial risk of death during severe exacerbations, and underlying cardiovascular risk, suggesting that cardiac risks need to be considered and reviewed in this patient population.

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

Laura J. Spece, MD, MS; William G. Weppner, MD, MPH; Bryan J. Weiner, PhD; Margaret Collins, PhD; Rosemary Adamson, MB, BS; Douglas B. Berger, MD, MLitt; Karin M. Nelson, MD, MSHS; Jennifer McDowell, BS; Eric Epler, BS; Paula G. Carvalho, MD; Deborah M. Woo, PharmD; Lucas M. Donovan, MD, MS; Laura C. Feemster, MD, MS; David H. Au, MD, MS; George Sayre, PsyD

Individuals with COPD typically rely on primary care clinics to manage their condition, and many do not see a pulmonary specialist. In a recent clinical trial (prior to our study), researchers tested a new tool that connects a pulmonary team with primary care providers to care for patients after they have been in the hospital for COPD. It used the electronic health record system (an e-consult). Individuals had improved symptoms of COPD when their primary care provider used the tool compared to those whose providers did not use the tool. We conducted our study to understand what primary care providers thought of the process so that we understand how the process could be improved.

We studied primary care providers who used the electronic health record tool to care for patients with COPD. We interviewed and surveyed the primary care providers after they used the tool. Primary care providers reported a positive experience, and they appreciated the help from the pulmonary team for COPD. Primary care providers had some concerns about communicating the note from the pulmonary team to their patient.

This study shows that pulmonary teams can help patients with COPD by teaming up with primary care providers through the electronic health record system and e-consults.

A Model to Predict Residual Volume from Forced Spirometry Measurements in Chronic Obstructive Pulmonary Disease

John W. Evankovich, MD; S.M. Nouraie, MD; Frank C. Sciurba, MD

Hyperinflation of the lungs is a feature related to many bothersome symptoms associated with chronic obstructive pulmonary disease (COPD). Lung hyperinflation drives shortness of breath, exercise limitation, and relates to poorer long-term outcomes for patients. Importantly, patients with lung hyperinflation are most likely to benefit from lung volume reduction procedures – whether accomplished via surgery or by newer, less-invasive techniques. Lung hyperinflation is most effectively measured in a device which measures trapped air, called a body plethysmograph. However, these devices are not routinely available in many hospitals and clinics. By contrast, nearly all COPD patients have access to standard lung function spirometry tests to measure forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). In our study we used data from two groups of patients with COPD to determine if lung hyperinflation could be predicted from simple spirometry alone. We found a calculation using only a combination of age, sex, and spirometry (FVC and FEV1) that is quite accurate at predicting lung hyperinflation in COPD patients. These results could help identify patients with lung hyperinflation who do not have formal lung volume measurements. This information could affect the decisions made about their care and could also help in referrals for possible lung volume reduction procedures.

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

Laura C. Myers, MD, MPH; Richard K. Murray, MD; Bonnie M.K. Donato, PhD; Vincent X. Liu, MD, MSc; Patricia Kipnis, PhD; Asif Shaikh, MD, DrPH; Jessica Franchino-Elder, PhD, MPH

Sometimes patients with chronic obstructive lung disease (COPD) are on steroid medications, either in the form of pills or inhalers. We wanted to find out whether patients exposed to these steroids in the year or month leading up to getting coronavirus disease 2019 (COVID-19) made them more likely to be admitted to the hospital as a result of the virus. Knowing this information might change how we prescribe these medications during the pandemic. We did not find that patients exposed to steroids in the year or month before getting COVID-19 made them more likely to be admitted to the hospital. We recommend continuing to prescribe these medications in accordance with current clinical guidelines.

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, PhD

After patients with chronic obstructive pulmonary disease (COPD) are treated in a hospital they sometimes need a second hospital stay (called a readmission). This is not good for the patient and is expensive. Many different health care providers are involved in the treatment of patients with COPD. If they know each other (we call this provider connectedness), medical information can be better communicated between the health care providers and the care provided seems seamless (this is called “continuity of care”). To find out how well health care providers know each other we used a social network analysis method. The data comes from a large database that was provided by a health insurance company in Germany. We looked at whether connections between different types of health care providers—general practitioners and specialists—were related to better continuity of care and fewer readmissions to the hospital for patients with COPD. We found that how well providers were connected was related to the chance for patients to be readmitted a second time to the hospital, but this was only a small effect. Because of the small effects, more research is needed before recommendations for changes in health care can be made.

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

Loes Oostrik, MSc; Jean Bourbeau, MD, MSc; Dany Doiron, PhD; Bryan Ross, MD, MSc; Pei Zhi-Li, MSc; Shawn D. Aaron, MD; Kenneth R. Chapman, MD, MSc; Paul Hernandez, MDCM; François Maltais, MD; Darcy D. Marciniuk, MD; Denis O’Donnell, MD; Wan C. Tan, MD; Don D. Sin, MD, MPH; Brandie Walker, MD, PhD; Tania Janaudis-Ferreira, PhD, MSc

Being physically active is difficult for people with chronic obstructive pulmonary disease (COPD) because of symptoms like shortness of breath, fatigue, and muscle weakness. Being inactive may increase the risk of disease progression.

We studied the levels of physical activity of people with a mild version of COPD and which factors influence their levels of physical activity. It was assumed that people who had a high symptom burden (how severe the symptoms are and how often they occur) would be less active because of breathlessness. This was studied in a population of 1500 participants from the Canadian Cohort of Obstructive Lung Disease (CanCOLD) with and without COPD, including people who were newly diagnosed. Using questionnaires, we measured how much symptom burden they felt and how active they were in a typical week. The results showed that people with a high symptom burden were less active, even with mild COPD.

Our work highlights the importance of screening this group of people (with mild COPD) and offering an intervention to help them cope with the disease and be more physically active.

Ambient Air Pollution Exposure and Sleep Quality in COPD

Mudiaga O. Sowho, MD, MPH; Abigail L. Koch, MD; Nirupama Putcha, MD, MHS; Han Woo, PhD; Amanda Gassett, MS; Laura M. Paulin, MD, MHS; Kirsten Koehler, PhD; R. Graham Barr, MD; Alejandro P. Comellas, MD; Christopher B. Cooper, MD, PhD; Igor Barjaktarevic, MD; Michelle R. Zeidler, MD; Martha E. Billings, MD, MS; Russell P. Bowler, MD, MPH; MeiLan K. Han, MD, MS; Victor Kim, MD; Robert Paine III, MD; Trisha M. Parekh, DO, MSPH; Jerry A. Krishnan, MD, PhD; Stephen P. Peters, MD, PhD; Prescott G. Woodruff, MD, MPH; Aaron M. Baugh, MD; Joel D. Kaufman, MD, MPH; David Couper, PhD; Nadia N. Hansel, MD, MPH

Poor sleep quality is common in COPD patients who are also vulnerable to air pollution exposure. In this study, we explored the relationship between air pollution exposure and sleep quality in COPD patients. We found that exposure to air pollution increases the risk for poor sleep quality in COPD patients, particularly those who currently smoke and those who are overweight-obese. We found that obese females experience the most effects of air pollution. Although poor sleep quality is common in COPD, our results suggest that exposure to air pollution is a potential contributor. For COPD patients, reducing air pollution exposure may help improve sleep health and their overall quality of life. These findings lay the groundwork for future research that will explore the impact of air pollution exposure on sleep health, not just in patients with chronic respiratory disorders like COPD, but also in the general population.

Associations Between Muscle Weakness and Clinical Outcomes in Current and Former Smokers

Richard H. Zou, MD; S. Mehdi Nouraie, MD, PhD; Harry B. Rossiter, PhD; Merry-Lynn McDonald, PhD, MS; Dawn L. DeMeo, MD, MPH; Stefanie Mason, MD; George R. Washko, MD; Punam K. Saha, PhD; Barry J. Make, MD; Richard Casaburi, PhD, MD; Elizabeth A. Regan, MD, PhD; Jessica Bon, MD, MS; for the COPDGene Investigators

Muscle weakness is a common feature of chronic obstructive pulmonary disease (COPD). In smokers, muscle weakness is associated with worsening lung disease, poor function and mobility, reduced quality of life, and an increased risk of death. There is limited data describing muscle weakness in smokers with a normal spirometry test and in smokers with what is called a preserved ratio-impaired spirometry (PRISm). PRISm means that the individual has one lung function test, commonly associated with COPD, that is normal (forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] ratio) and one test that is not normal (FEV1) Identifying muscle weakness in all smokers is important to allow for early treatment. The purpose of this study was to compare two easy-to-perform measures of muscle weakness—the sit-to-stand test and the handgrip strength test—with important clinical outcomes in smokers with COPD who have normal spirometry, and with smokers who are classified as having PRISm. Our study demonstrated that poorer performance on the sit-to stand test and the hand grip test was associated with worse lung function, quality of life, severe exacerbations, and survival. These findings highlight the importance of screening all smokers for muscle weakness in the outpatient setting.

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

Nawaf M. Alotaibi, MD, MSc; Sheena Tam, BSc; Stephan F. van Eeden, MD; Tawimas Shaipanich, MD; Stephen Lam, MD; Janice M. Leung, MD; Don D. Sin, MD, MPH

In this study, we have collected washings from the lungs of stable COPD patients using a bronchoscope. We did this to test if there was an association between having a positive result for either a bacteria, fungus, or virus and a patient’s quality of life. We also tested the lung washings for high levels of white blood cells, a marker of active inflammation. Interestingly, we found that approximately 50% of stable patients with COPD had bacteria and/or a virus detected in their lungs. This was associated with high levels of white blood cells and poor quality of life. The exception to this was the bacteria called Haemophilus influenzae. These bacteria did not produce a high white blood cell count in the lungs or affect the quality of life to the same extent as other bacteria/viruses. In addition, we have found that testing positive for a bacteria or virus other than Haemophilus was strongly associated with lung inflammation, regardless of a patient’s smoking history or the level of severity of their COPD. These findings suggest that targeting those patients who have a positive result for microbes, other than Haemophilus, with antibiotic and/or anti-inflammatory therapy may lead to better outcomes in stable COPD patients.