Table2_Energy cost of walking in obese survivors of acute lymphoblastic leukemia: A report from the St. Jude Lifetime Cohort.docx

PurposeAdult survivors of childhood acute lymphoblastic leukemia (ALL) have impaired adaptive physical function and poor health-related quality of life (HRQoL). Obesity may contribute to these impairments by increasing the physiological cost of walking. Due to treatment exposures during ALL therapy, survivors’ cost of walking may be more impacted by obesity than the general population. Therefore, we examined associations between obesity, persistent motor neuropathy, and energy cost of walking; and examined associations between energy cost of walking, adaptive physical function, and HRQoL, in adult survivors of childhood ALL vs. community controls.
MethodsObesity was measured via body mass index (BMI) and body fat percentage. The physiological cost index (PCI) was calculated from the six-minute walk test. Adaptive physical functioning was measured using two tests: the timed up and go (TUG) test and the physical performance test. Persistent motor neuropathy was measured using the modified total neuropathy score; HRQoL was measured using the Short-Form-36 questionnaire. The associations between obesity and PCI were evaluated using multivariable linear regressions in adult survivors of childhood ALL (n = 1,166) and community controls (n = 491). Then, the associations between PCI, adaptive physical functioning and peripheral neuropathy were examined using multivariable linear regressions. Finally, to determine the association between obesity, and neuropathy on PCI, while accounting for potential lifestyle and treatment confounders, a three model, sequential linear regression was used.
ResultsObese individuals (BMI > 40 kg/m2 and excess body fat percentage [males: >25%; females: >33%]) had higher PCI compared to those with normal BMI and body fat percentage (0.56 ± 0.01 vs. 0.49 ± 0.009 beats/meter p < .01; and 0.51 ± 0.007 vs. 0.48 ± .0006 beats/meter p < .01, respectively). Treatment exposures did not attenuate this association. Increased PCI was associated with longer TUG time in survivors, but not community controls (6.14 ± 0.02 s vs. 5.19 ± 0.03 s, p < .01). Survivors with PCI impairment >95th percentile of community controls had lower HRQoL compared to un-impaired ALL survivors: 46.9 ± 0.56 vs. 50.4 ± 1.08, respectively (p < .01).
ConclusionObesity was associated with increased PCI. Survivors with high PCI had disproportionately worse adaptive physical function and HRQoL compared to controls. Survivors with increased energy costs of walking may benefit from weight loss interventions.

研究目的：儿童急性淋巴细胞白血病（acute lymphoblastic leukemia, ALL）成年幸存者存在适应性躯体功能受损及健康相关生存质量（health-related quality of life, HRQoL）不佳的问题。肥胖可通过增加步行生理成本加剧上述功能损害。由于ALL治疗期间的治疗暴露因素，该类幸存者的步行成本受肥胖的影响程度或高于普通人群。因此，本研究旨在对比儿童ALL成年幸存者与社区对照人群，分析肥胖、持续性运动神经病与步行能量成本之间的关联，同时探讨步行能量成本、适应性躯体功能与HRQoL之间的关联。

研究方法：本研究通过体重指数（body mass index, BMI）与体脂百分比评估肥胖程度；基于六分钟步行试验计算生理成本指数（physiological cost index, PCI）。适应性躯体功能采用两项测试评估：计时起立行走（timed up and go, TUG）测试与躯体功能测试。持续性运动神经病采用改良总神经病评分评估，HRQoL采用简明健康调查问卷（Short-Form-36 questionnaire）评估。首先，在儿童ALL成年幸存者（n=1166）与社区对照人群（n=491）中，采用多变量线性回归分析肥胖与PCI的关联；随后，采用多变量线性回归分析PCI、适应性躯体功能与周围神经病之间的关联；最后，为明确在控制潜在生活方式与治疗混杂因素的前提下，肥胖与神经病对PCI的联合影响，本研究采用三模型序贯线性回归进行分析。

研究结果：肥胖个体（BMI>40kg/m²且体脂百分比超标：男性>25%，女性>33%）的PCI水平显著高于BMI与体脂百分比正常的个体（分别为0.56±0.01 vs 0.49±0.009 次/米，p<0.01；0.51±0.007 vs 0.48±0.0006 次/米，p<0.01），且治疗暴露未削弱该关联。在ALL幸存者中，PCI升高与更长的TUG测试时长相关，但该关联未在社区对照人群中观察到（6.14±0.02s vs 5.19±0.03s，p<0.01）。PCI水平高于社区对照人群95百分位数的ALL幸存者，其HRQoL评分显著低于PCI未受损的ALL幸存者（46.9±0.56 vs 50.4±1.08，p<0.01）。

研究结论：肥胖与PCI升高显著相关。与对照人群相比，PCI升高的ALL幸存者其适应性躯体功能与HRQoL受损程度更为显著。步行能量成本升高的ALL幸存者或可从减重干预中获益。