Patients with COPD who experience recurrent exacerbations (frequent exacerbators) are recognized as a distinct clinical phenotype requiring targeted treatment, explains Alex Jenkins, PhD. Although evidence suggests that COPD exacerbations play a key role in poor pulmonary rehabilitation completion, whether frequent exacerbators are more likely to drop out of pulmonary rehabilitation is unclear. “And although observational evidence suggests that pulmonary rehabilitation can help reduce COPD exacerbation incidence, the underlying mechanisms behind this are unclear,” adds Dr. Jenkins. With research in healthy populations indicating that moderate exercise can help reduce respiratory infection risk—suggested to be due to the immune-enhancing effects of exercise—Dr. Jenkins and colleagues felt translating these findings to patients with COPD may provide a mechanistic link underpinning the observational evidence base to date.

Comparing Pulmonary Rehabilitation Responses

For a study published in COPD, the researchers sought to explore how frequent exacerbators responded to pulmonary rehabilitation, in terms of clinical outcome and immune responses, compared with patients with COPD who do not experience recurrent exacerbations. Based on past-year exacerbation history, participants with mild-very severe COPD (FEV1 pred, 52 ± 18%) were categorized as frequent (≥2 exacerbations/year) or infrequent (≤1 exacerbation/year) exacerbators. “We were particularly interested in examining the responses in a clinical setting so that we could show clinical applicability of our findings,” Dr. Jenkins says. “To do this, we took blood samples at the first and last class of a community pulmonary rehabilitation program for the assessment of inflammatory markers, as well as collected clinical outcomes (eg, exercise capacity and health-related quality of life) from initial and final assessments for analysis.”

Both frequent and infrequent exacerbators benefitted from pulmonary rehabilitation in similar fashion—as defined by improvements in classic clinical outcomes such as exercise capacity and health-related quality of life—and should be referred for treatment if eligible, stresses Dr. Jenkins. “However, our findings show that frequent exacerbators of COPD are less likely to complete pulmonary rehabilitation,” he adds. “Also, in terms of immune responses, we found that pulmonary rehabilitation reduced inflammatory markers more in the frequent exacerbators group, which warrants further attention in defining the mechanistic link between pulmonary rehabilitation and a reduced incidence of exacerbations. Based on this data, pulmonary rehabilitation may stand to have anti-inflammatory properties, especially in phenotypes characterized as having heightened inflammation (ie, frequent exacerbators).”

Dr. Jenkins notes that leukocyte and neutrophil counts—inflammatory markers known to be influenced by exercise in health populations—were reduced with pulmonary rehabilitation in frequent exacerbators of COPD only (Table). “Despite no significant differences between the groups in terms of basal inflammation, this could be attributed to the visually higher leukocyte and neutrophil counts in frequent exacerbators at baseline,” he says. “Other blood cell counts, including lymphocytes, eosinophils, and neutrophil/lymphocyte ratio, were not significantly affected by pulmonary rehabilitation. Those with heightened basal inflammation stand to have the greatest reductions in inflammatory cells counts with pulmonary rehabilitation.”

Looking to the Future

The main message from the study findings, according to Dr. Jenkins, is that all who need pulmonary rehabilitation should be referred for treatment, given the outlined benefits for both frequent and infrequent exacerbators of COPD. He notes, however, that frequent exacerbators of COPD may need extra support to aid completion of pulmonary rehabilitation.

“From a research perspective, it is too early to suggest what these approaches may be, and the same applies to interpreting the immune responses to rehabilitation in a clinical context,” says Dr. Jenkins. “The immune response to exercise aspect is a hypothesis-generating area currently, with much high-quality research required before any evidence can be applied to a clinical context. There is a clear shift in the field of pulmonary rehabilitation research to looking at approaches for characterizing people with COPD into subgroups based on clinical needs associated with disease characteristics. It is accepted that subsets of people with COPD do not respond as well to pulmonary rehabilitation, and it is important to identify the traits underpinning this, so that treatment can be better tailored and personalized.”