COPDの栄養状態：低酸素の役割

COPDの栄養状態：低酸素の役割というレビュー論文を紹介します。

Comasia A. Raguso, and Christophe Luthy: Nutritional status in chronic obstructive pulmonary disease: Role of hypoxia. Nutrition (2010), doi:10.1016/j.nut.2010.07.009

COPDでは悪液質の患者が少なくなく、栄養障害を認めることが多いです。その要因の1つとして、この論文では低酸素に焦点を当てています。図に示すように低酸素のために、食思不振、炎症、筋繊維のタイプ変化などが生じ、その結果、食事摂取量低下や筋肉の機能不全がおこり悪液質となるというメカニズムが提案されています。

またインシュリン抵抗性だけでなく成長ホルモン抵抗性がおこるため、蛋白分解が増加して筋肉の機能不全がおこるというメカニズムも提案しています。

COPDへの介入として、エネルギー摂取量の増加だけでは栄養状態の改善は得られません（コクラン）。グレリンは今後期待されていますが、同化ホルモン（テストステロンなど）は推奨できません。運動療法（レジスタンストレーニングと有酸素運動）は有効です。

低酸素が悪液質の引き金になっているのであれば、早期在宅酸素療法が悪液質の予防に有効な可能性があります。一方、酸化ストレスも問題になりますので、過度の酸素療法も逆効果となる可能性があります。酸素飽和度でいくつがベストなのかという指標を私は知りませんが、80台でも100でもないことは確かだと思います。

Abstract
In patients with chronic obstructive pulmonary disease (COPD), malnutrition and limited physical activity are very common and contribute to disease prognosis, whereas a balance between caloric intake and exercise allows body weight stability and muscle mass preservation. The goal of this review is to analyze the implications of chronic hypoxia on three key elements involved in energy homeostasis and its role in COPD cachexia. The first one is energy intake. Body weight loss, often observed in patients with COPD, is related to lack of appetite. Inflammatory cytokines are known to be involved in anorexia and to be correlated to arterial partial pressure of oxygen. Recent studies in animals have investigated the role of hypoxia in peptides involved in food consumption such as leptin, ghrelin, and adenosine monophosphate activated protein kinase. The second element is muscle function, which is strongly related to energy use. In COPD, muscle atrophy and muscle fiber shift to the glycolytic type might be an adaptation to chronic hypoxia to preserve the muscle from oxidative stress. Muscle atrophy could be the result of a marked activation of the ubiquitin-proteasome pathway as found in muscle of patients with COPD. Hypoxia, via hypoxia inducible factor-1, is implicated in mitochondrial biogenesis and autophagy. Third, hormonal control of energy balance seems to be affected in patients with COPD. Insulin resistance has been described in this group of patients as well as a sort of “growth hormone resistance.” Hypoxia, by hypoxia inducible factor-1, accelerates the degradation of tri-iodothyronine and thyroxine, decreasing cellular oxygen consumption, suggesting an adaptive mechanism rather than a primary cause of COPD cachexia. COPD rehabilitation aimed at maintaining function and quality of life needs to address body weight stabilization and, in particular, muscle mass preservation.