Comorbidities Among Patients With COPD Impact Outcomes, Require Further Research

A symposium at the 2023 American Thoracic Society (ATS) International Conference encouraged attendees to “think outside the lung,” with expert presenters giving overviews of common comorbidities that warrant consideration in patients who present with chronic obstructive pulmonary disease (COPD).

The session broadly discussed the burden of comorbidities in COPD and highlighted 3 common comorbidities: anxiety and depression, cardiovascular disease, and skeletal muscular dysfunction. Challenges and opportunities for screening patients with COPD for comorbidities were also a focus of the presentation.

Miguel J. Divo, MD, MPH, assistant professor of medicine at Harvard and clinician at Brigham and Women’s Hospital in Boston, MA, gave insight into the occurrence of comorbidities overall in COPD and their impact on patient outcomes.

“Roughly, every patient that we diagnose is going to have between 4 to 6 different co-occurring diseases, and this is not accounting for COPD," Divo said, citing a study of 27,000 patients in Spain. "From there, we need to then ask the question, ‘Is this unique for COPD?’” When compared with a cohort of the same size comprised of people without a COPD diagnosis, those with COPD had 2 more comorbidities than those without COPD regardless of age group, he explained.

What’s more, these comorbidities were happening roughly 15 years earlier in individuals with COPD vs those not diagnosed with COPD, he said.

Divo also highlighted data on quality of life and mortality showing that as the number of comorbidities increases, the probability of worse quality of life is higher. Additionally, having more comorbidities has been directly associated with increased mortality, he said.

“So what are the culprits? If I take a lot of those studies that I'm mentioning [and] all the other different aspects of patient-centered outcomes, these are the big players: cancer, cardiovascular disease, musculoskeletal disease, metabolic and endocrinopathies, and mental health.”

COPD and Mental Health

Anxiety and depression in COPD are crucial comorbidities to examine, as they are very prevalent in the population overall, said Victor Kim, MD, FAASM, professor of thoracic medicine and surgery at Temple University in Philadelphia, PA. While evidence supports a link between mood disorders and COPD, anxiety and depression may be underdiagnosed in clinical settings, he said.

“Despite the commonness, half of those individuals with anxiety and depression don't seek pharmacologic treatment. And from the standpoint of a doctor concentrating on pulmonary diseases, it may be under-recognized or deprioritized by the patient and clinician,” Kim said.

The prevalence of depression is even higher in those with COPD, Kim noted, highlighting an analysis in which 26% of a cohort of individuals with COPD reported depressive symptoms, compared with 12% and 7% of smokers and non-smokers, respectively. In a matched cohort, signs of depression were significantly more common in those with airflow obstruction.

In the cohort, depressive symptoms were more common in individuals with post airflow obstruction, current smokers, females, and younger vs older patients. Other cohorts replicate similar data in terms of depression symptom prevalence in COPD, Kim said.

In another study, anxiety and depression were shown to be more common among those with more severe respiratory symptoms and exacerbations based on Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) scores, Kim said. And depression is associated with other outcomes, he noted.

For example, one study uncovered an interesting correlation between 6-minute walk distance test results and depression. While patients in the study only showed minor differences in lung function, those with depression walked about 50 meters less than individuals without depression.

Comorbid anxiety and depression may also be predictive of respiratory exacerbations, according to research in 2 large cohorts of COPD patients. Patients with both anxiety and depression showed an increased risk of exacerbations, Kim explained. In other treatment settings, such as cardiovascular disease, mood disorders are also thought to translate to worse outcomes.

With current data in mind, Kim concluded that treating the whole patient with comorbidities in mind is key for improving outcomes in respiratory conditions and other diseases.

Cardiovascular Disease and COPD

It has long been known that cardiovascular disease is a common occurrence among patients with COPD, and their co-occurrence is often the subject of research. Yet, not much is being done to advance the management of parallel COPD and cardiovascular disease, explained Jennifer K. Quint, PhD, FRCP, MSc, professor of respiratory epidemiology at Imperial College London in the United Kingdom.

A number of underlying risk factors contribute to the co-occurrence of cardiovascular disease and COPD, including smoking, physical inactivity, diet, air pollution, and more.

“This all leads to accelerated inflammation,” Quint said. “We also know that COPD itself, as it worsens, can potentially impact on cardiovascular disease.”

The current guidelines for treating cardiovascular disease in patients with COPD are clear and recommend treating it the way any cardiovascular disease case would be treated, but research has shown that those with both conditions do not receive beta blockers for cardiovascular conditions as often as those who do not have co-occurring COPD.

Due to the overlapping mechanisms of the conditions, some of the treatments used for COPD may impact cardiovascular diseases, and treatments for cardiovascular disease may impact COPD, she noted. Research in this area is important, with some past research suggesting that some treatments for COPD may be protective from a cardiovascular standpoint, Quint said.

While such concepts have been reported time and again, the crucial next step is determining how care can be tailored to these conditions when they occur simultaneously. In the same vein, Quint noted that because there is substantial overlap in the biological mechanisms and risk factors for COPD and cardiovascular disease, research into how cardiovascular disease more easily in the COPD population is needed.

“If we don't diagnose it and we don't manage it, then we're not going to be able to ultimately change the outcomes,” she said.

Skeletal Muscle Dysfunction and COPD

Harry B. Rossiter, PhD, a researcher at the Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Center in Torrance, CA, began his portion of the presentation by noting that 12%-40% of patients with COPD experience muscle loss and weakness and explaining a cycle of muscle loss that these patients can fall into.

“Typically, when we're thinking about COPD and skeletal muscle, we think about the fact that these patients have dyspnea on exertion of forced inactivity, which leads to muscle wasting, which in turn causes an increased ventilator demand,” Rossiter said. “So these patients have both higher ventilator demands and low ventilatory capacity.”

The implications of muscle loss can be serious, he added, highlighting a study of nearly 200,000 hospital admissions that found about 10% of COPD patients to express a muscle loss phenotype, which was also the second strongest predictive variable for increased length of stay for patients with COPD exacerbations.

Inactivity is not the only mechanism behind muscle wasting, Rossiter explained, and inactivity alone does not explain the loss of muscle mass and mitochondrial function that COPD patients experience. While a number of factors may come into play, the mechanisms are not entirely clear yet.

As for potential treatments to break the cycle of muscle loss and weakness in patients with COPD, Rossiter noted that he has worked on clinical trials involving myostatin inhibitors and selective androgen receptor modulators. In his experience with clinical trials, he has found that adding exercise to drug interventions for muscle mass loss is key for simultaneous muscle strength building.

Screening Potential and Barriers to Implementation

While it would be ideal to simply screen all patients diagnosed with COPD for known comorbidities to facilitate timely and beneficial treatment, implementing such a widespread process is easier said than done, said Jessica Bon, MD, MS, associate professor of medicine in the Division of Pulmonary, Allergy and Critical Care Medicine at the University of Pittsburgh in Pittsburgh, PA.

Reiterating the prevalence of comorbidities in patients with COPD, Bon noted that the guidelines for screening among these patients are vague. While GOLD now discusses comorbidities such as cardiovascular disease and osteoporosis comprehensively and recognizes that they occur at all severities of COPD, the screening guidelines essentially stop there, Bon said.

“The problem is we know that some of these comorbidities are high risk, and the general guidelines may not be enough,” Bon said, and added that the comorbidities discussed in the session remain underdiagnosed.

Going forward, the development of widespread, appropriate, cost-effective screening protocol is needed to mitigate gaps in the identification of comorbidities in patients with COPD.