LAUSR

To the Editor: In a previous issue of CHEST (December 2017), Moore et al1 published a large-scale cohort study of electronic health records reporting COPD patients referred for (but who did not necessarily complete) pulmonary rehabilitation did not experience fewer general practitioner visits and hospitalizations compared with those not referred.1 Conversely, the latest findings from a UK (National) COPD Pulmonary Rehabilitation Audit highlighted that completion of pulmonary rehabilitation is associated with reduced risk of hospitalization and time spent in hospital.2 Reductions in hospital admissions and bed days were larger in those attending more sessions and/or receiving longer programs. Subsequently, we have published a meta-analysis of randomized controlled trials suggesting that the addition of supervised maintenance exercise programs following pulmonary rehabilitation decreases the risk of hospital admissions (respiratory cause) and exacerbations requiring treatment.3 Taken together, the available evidence raises the important role that exercise independently, or within pulmonary rehabilitation, can play in reducing health care use. The underlying mechanisms of action, however, remain poorly understood. An editorial published in response to Moore et al1 suggested that pulmonary rehabilitation (exercise) does not plausibly affect the frequency of inflammatory and infectious events but leads to reduced severity or better management of exacerbations via changes in dyspnea, physical conditioning, and enhanced disease knowledge.4 Although we agree that these mechanisms may be partly responsible, the additional impact of supervised maintenance exercise programs following pulmonary rehabilitation is suggestive of other unexplored mechanisms on health care use outcome data collected in the postrehabilitation period. The evidence demonstrating the immune-regulatory and anti-inflammatory effects of regular exercise as part of short- and/or long-term training programs in older populations and those living with long-term conditions are well established.5 Although studies in COPD are lacking, absence of evidence is not evidence of absence. We currently have limited insight to confidently deny any plausible impact of exercise-based interventions, including pulmonary rehabilitation on the frequency of inflammatory and infectious events. Research is required using surrogate markers associated with exacerbation frequency or representing clinically relevant measures of immune function. Although the primary purpose of pulmonary rehabilitation may not be to affect health care use,2 increasing evidence suggests that exercise (the cornerstone of pulmonary rehabilitation) plays a role in prevention and management of such outcomes. Unlike pharmacological approaches that continue to be studied and recommended as the key interventions in prevention of exacerbations/hospitalizations, rigorous scientific investigation of the underpinning mechanisms of exercise-based treatment is lacking. In fact, we have barely scratched the surface.