探討身體組成及阻抗相位角在肺阻塞病人的臨床重要性

Abstract

研究背景 肌少症是肺阻塞的常見共病症之一。肌少症的病人肌肉力量及肌肉的質量都同時下降，目前被證實與不良的臨床預後相關。然而，力弱症，即病人肌肉力量下降但肌肉質量維持正常，以及前肌少症，即病人肌肉質量下降但肌肉力量維持正常，皆鮮少被提及，對肺阻塞病患的臨床預後的影響也未知。而除了身體質量指數、肌肉量、肌力…等指標外，全身相位角在許多疾病發現與身體組成的變化及臨床預後相關。這個新興非侵入性的生物指標在肺阻塞很少提及，目前也沒有分界點提供臨床運用。因此本研究將研究力弱症、前肌少症、肌少症對臨床的影響以及全身相位角的臨床運用。 研究假說 此研究將探討力弱症、前肌少症是否與肌少症同樣與肺阻塞病患不良的預後相關。此外，研究將尋找全身相位角評估肌少症的臨床切點，並探討全身相位角在肺阻塞病患照護的臨床運用。 研究方法 這個前瞻性的研究在台大醫院進行收案。力弱症定義為肌肉量維持(男≥ 7.0 kg/m2;女≥ 5.7 kg/m2)但握力下降(男< 28 kg;女< 18 kg)；前肌少症則定義為握力維持(男≥ 28 kg;女≥ 18 kg)但肌肉量下降(男< 7.0 kg/m2;女< 5.7 kg/m2)；肌少症則定義為肌肉量及握力皆下降。全身相位角的臨床切點則以預測肌少症的ROC曲線來進行評估。本研究以6分鐘步行和簡易身體功能評估(Short Physical Performance Battery, SPPB)來衡量受試者的身體功能。 研究結果 本研究共招募了494位的受試者。對照組有211位、前肌少症組有59位、力弱症組有111位及肌少症組有113位。前肌少症以及肌少症兩組相較對照組的身體質量指數較低，腰圍則較小。肌少症組相較其他三組在症狀上較嚴重、肺功能也較差，然而前肌少症以及力弱症組則與對照組相仿。前肌少症、力弱症組和肌少症組6分鐘步行距離皆較對照組短(381.1公尺、348.7公尺, 304.4公尺, 420公尺, p<0.001)。而前肌少症組以及肌少症組有較多病人有嚴重的運動引起的低血氧。此外，力弱症組相較於對照組有較多的功能下降。肌少症組相較前肌少症組、力弱症組及對照組有較高的死亡率(對照組:6.2% vs.前肌少症組: 10.2% vs. 力弱組:9.0% vs. 肌少症組: 25.7%, p<0.05)。經校正年齡、肺功能及Charlson共病指標後，僅肌少症是死亡率的顯著危險因子(危險比: 2.11; 95% CI 1.04-4.28)。 研究利用預測肌少症的ROC曲線找到全身相位角的臨床切點。在男性分別是4.8而女性是4.1。全身相位角數值低於切點的病人相對高於切點的病人有較嚴重的臨床症狀、較差的身體功能表現以及較高的嚴重急性惡化以及死亡率。經校正年紀、性別、身體質量指數、Charlson’s共病指標以及第一秒用力呼氣量，全身相位角在嚴重急性惡化及死亡率上是重要的預測因子。而與身體質量指數、無脂肪質量指數及握力相比，全身相位角在死亡率上能當作良好的預測指標。 研究結論 在肺阻塞的病人中，除了肌少症組，前肌少症組及力弱組無論在肺功能、症狀或臨床預後上皆與對照組相仿。然而，前肌少症組有較多的運動引起的嚴重低血氧狀況。此外，力弱症組相較對照組有較嚴重的身體功能上的下降。全身相位角是一個新穎的肺阻塞指標，在預後的評估上優於身體質量指數及無脂肪肌肉量。低全身相位角的病患不論在臨床症狀、功能以及預後上都較正常的全身相位角來得嚴重。未來進一步的縱貫研究將更能了解此生物指標的臨床運用。

Background Changes in body composition are common in patients with chronic obstructive pulmonary disease (COPD). Sarcopenia, the presence of muscle weakness, and muscle loss has been shown to be a poor prognostic factor. However, little is known about the impact of pre-sarcopenia, the presence of muscle loss but preserved muscle strength, and dynapenia, the presence of muscle weakness, and preserved muscle mass. Besides, whole-body phase angle, a novel biomarker proven to be closely related to body composition change and prognosis had rarely been explored in COPD. Hypothesis Pre-sarcopenia, dynapenia, similar to sarcopenia, may be associated with poor clinical outcomes. A cut-off value for the whole-body phase angle may exist, and a low whole-body phase angle may be associated with poor clinical outcomes. Methods This prospective study enrolled patients with spirometry-confirmed COPD at National Taiwan University Hospital. Pre-sarcopenia was defined as decreased fat-free mass (M: < 7.0 kg/m2, F: < 5.7 kg/m2) but preserved handgrip strength (M: ≥ 28 kg, F: ≥18 kg); dynapenia was defined as preserved fat-free mass (M: ≥ 7.0 kg/m2, F: ≥ 5.7 kg/m2) but decreased handgrip strength (M: < 28 kg, F: < 18 kg); whereas sarcopenia was defined as a decrease in both dimensions. The cut-off value of the whole-body phase angle was determined using the receiver operating characteristic curve (ROC) to predict the presence of sarcopenia stratified by sex. Physical function was evaluated using a 6-minute walk test and the Short Physical Performance Battery (SPPB). Results A total of 494 patients were enrolled: 211 in the control group, 59 in the pre-sarcopenia group, 111 in the dynapenia group, and 113 in the sarcopenia group. The dynapenia group, similar to the sarcopenia group, had shorter 6-minute walk distances and worse SPPB scores than the control group. Patients with pre-sarcopenia, similar to those with sarcopenia, were prone to severe exercise-induced desaturation. The two-year mortality was similar in the control, pre-sarcopenia, and dynapenia groups but considerably lower than that in the sarcopenia group (6.2% vs. 10.2% vs. 9.0% vs. 25.7%, p<0.05). Univariable and multivariable analysis showed that only sarcopenia was associated with an increased risk of mortality (odds ratio: 2.11; 95% CI 1.04-4.28). The cutoff value of the whole-body phase angle to predict sarcopenia was 4.8 for men and 4.1 for women. Patients with a whole-body phase angle lower than the cutoff value presented with more severe symptoms, worse functional performance, and a significantly higher risk of severe acute exacerbation and mortality than those with a whole-body phase angle higher than the cutoff value. After adjusting for age, sex, BMI, Charlson’s comorbidity index, and FEV1, the whole-body phase angle remained an independent risk factor for severe acute exacerbation and mortality. Furthermore, whole-body phase angle is the only anthropometric parameter suitable as a biomarker for acute exacerbation and mortality compared to BMI, fat-free mass index, and handgrip strength. Conclusion & Future Work Among patients with COPD, aside from the sarcopenic group, the pre-sarcopenia and dynapenia groups had clinical outcomes similar to the control group. However, patients with dynapenia experience significant functional deterioration, whereas patients with pre-sarcopenia present with more severe exercise-induced desaturation. The whole-body phase angle is a potential biomarker for acute exacerbation and mortality in COPD. The longitudinal evaluation of this novel biomarker may provide further information on its utility in clinical practice.