PIH and sarcopenia in COPD: a causal relationship?

Article: Sarcopenia in chronic obstructive pulmonary disease: Skeletal muscle gasping for air?

Nocturnal hypoxia commonly occurs in patients with chronic obstructive pulmonary disease (COPD), and in this context may be referred to as prolonged intermittent hypoxia (PIH). It is estimated that 1 in 5 COPD patients also suffer from sarcopenia, which may affect both respiratory and non-respiratory skeletal muscles and be causally linked to PIH. The presentation of sarcopenia alongside COPD is known to reduce quality of life and increase both hospitalisation and mortality rates in affected patients. Despite this, the adaptive cellular responses to PIH in skeletal muscle have not yet been adequately investigated.

The aim of this article was to discuss findings from a 2022 paper by Attaway and colleagues, which itself aimed to explore adaptive cellular responses to PIH.

Key learnings:

The reviewed article validated a myotube model of PIH as a potential explanation for sarcopenic phenotypes in COPD. In essence, it posited that PIH’s contribution to sarcopenia occurs via the regulation of hypoxia-inducible factor 1 (HIF1), which is associated with protein synthesis inhibition and impairments in mitochondrial oxidative phosphorylation. However, whether these mechanisms are causally linked to sarcopenia remains unexplored. Mice models of PIH which adequately mimic COPD in humans were lacking in the reviewed study, which instead used chronic hypoxia models. Future studies in these animal models should further knock out HIF1 and other proposed transcription factors in a skeletal muscle-specific manner. Observations regarding protein synthesis and mitochondrial oxidative function in these models, along with the use of skeletal muscle biopsies from COPD patients, may greatly inform clinical understanding of the causal drivers of sarcopenia in COPD.

Reviewed by: S. Duarte

Authors: Johansen VBI

Published in: The Journal of Physiology 2023