COPD and Skeletal Muscle Mass: Discovering New Possibilities

Written by Amy Attaway, MD

Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death in the United States.1 Sarcopenia, or skeletal muscle loss, affects 20%-40% of COPD patients.2-4 It is a major comorbidity that impacts survival and physical function in COPD patients.5-9

We have previously demonstrated in the Nationwide Inpatient Sample that sarcopenia (defined by billing codes) is associated with increased risk for mortality (adjusted odds ratio [adj OR]: 2.1, 95% confidence intervals [CI]: 1.9-2.2) and higher healthcare costs (approximately 84% greater cost of hospitalization).10 As illustrated in the figure below, we have also demonstrated in our Cleveland Clinic population of COPD patients referred for lung volume reduction that reductions in the pectoralis muscle cross-sectional area are associated with disease progression in COPD (i.e., mortality, need for lung volume reduction or need for lung transplant).11 However, despite sarcopenia being a major problem for patients with COPD, the underlying mechanisms that cause sarcopenia remain poorly understood.12 Because of this, typical strategies to improve sarcopenia, including pulmonary rehabilitation and nutritional therapies, do not consistently improve outcomes for COPD patients.13

Why we care about hypoxia

The reason that COPD patients develop skeletal muscle loss is likely multifactorial and includes factors such as poor nutrition, aging, systemic inflammation and medications (i.e., corticosteroids).14 One of the areas in which we have focused our studies is the impact of hypoxia on skeletal muscle loss. While previous studies focused on the impact of continuous hypoxia on skeletal muscle loss, continuous hypoxia is a condition that is routinely screened for and treated in COPD patients per established guidelines.15 A more clinically relevant form of hypoxia that COPD patients routinely experience is a cycling of hypoxia/normoxia where COPD patients have normal oxygen saturation during the day but develop hypoxia while they are sleeping. Between 27% and 70% of COPD patients experience low oxygen saturation in the blood during sleep,16-18 and hypoxia can occur throughout sleep.19

Observational studies have demonstrated an increased risk for mortality due to nocturnal hypoxia;20 however, randomized controlled trials have not demonstrated a survival benefit from nocturnal oxygen supplementation.21-23 Because of this, current guidelines do not recommend screening for or treating nocturnal hypoxia unless patients report symptoms of poor sleep or have evidence of comorbidities such as pulmonary hypertension.24 However, other studies have suggested that nocturnal hypoxia may contribute to sarcopenia in COPD as demonstrated by: reductions in exercise work rate,25 six-minute walk test,26 skeletal muscle contraction of the diaphragm27 and overall increased systemic inflammation.28

A three-pronged approach to sarcopenia and future directions

Our approach to determining whether nocturnal hypoxia contributes to sarcopenia in COPD is three-pronged:

1. Determine whether sarcopenia is associated with nocturnal hypoxia in our Cleveland Clinic population of patients with COPD.
2. Utilize laboratory-based techniques to determine the mechanisms of sarcopenia due to hypoxia/normoxia cycling with in vitro and in vivo models of sarcopenia in COPD.
3. Develop and validate new therapies to improve sarcopenia in COPD using laboratory-based models that will translate to improving outcomes in COPD patients.

While our goal has been to determine the mechanisms of sarcopenia in COPD patients, our research has the potential for broad application because nocturnal hypoxia occurs in other pulmonary disorders associated with sarcopenia including interstitial lung disease and pulmonary hypertension.29-31

References

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