Normative Inter limb Impedance Ratios: Implications for Early Diagnosis of Uni and Bilateral, Upper and Lower Limb Lymphedema

Megan L. Steele, PhD, 1 Monika Janda, PhD, 1 Dimitrios Vagenas, PhD, 1 Leigh C. Ward, PhD, 2 Bruce H. Cornish, PhD, 1 Robyn Box, PhD, 3 Susan Gordon, PhD,4,5 Melanie Matthews, BPhysio (Hons), 4 Sally D. Poppitt, PhD, 6 Lindsay D. Plank, PhD, 7 Wilson Yip, MHSc, 6 Angela Rowan, MNutr, 8 Hildegard Reul-Hirche, DipPhty, 9 Andreas Obermair, MD,10 and Sandra C. Hayes, PhD1. Lymphatic Research Biology 2018

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Normative Interlimb Impedance Ratios: Implications for Early Diagnosis of Uniand Bilateral, Upper and Lower Limb Lymphedema

Megan L. Steele, PhD, 1 Monika Janda, PhD, 1 Dimitrios Vagenas, PhD, 1 Leigh C. Ward, PhD, 2 Bruce H. Cornish, PhD, 1 Robyn Box, PhD, 3 Susan Gordon, PhD,4,5 Melanie Matthews, BPhysio (Hons), 4 Sally D. Poppitt, PhD, 6 Lindsay D. Plank, PhD, 7 Wilson Yip, MHSc, 6 Angela Rowan, MNutr, 8 Hildegard Reul-Hirche, DipPhty, 9 Andreas Obermair, MD,10 and Sandra C. Hayes, PhD1. Lymphatic Research Biology 2018

Background: Bioimpedance spectroscopy detects unilateral lymphedema if the ratio of extracellular fluid (ECF) between arms or between legs is outside three standard deviations (SDs) of the normative mean. Detection of bilateral lymphedema, common after bilateral breast or gynaecological cancer, is complicated by the unavailability of an unaffected contralateral limb. The objectives of this work were to (1) present normative values for interarm, interleg, and arm-to-leg impedance ratios of ECF and ECF normalized to intracellular fluid (ECF/ICF); (2) evaluate the influence of sex, age, and body mass index on ratios; and (3) describe the normal change in ratios within healthy individuals over time.

Methods: Data from five studies were combined to generate a normative data set (n=808) from which mean and SD were calculated for interarm, interleg, and arm-to-leg ratios of ECF and ECF/ICF. The influence of sex, age, and body mass index was evaluated using multiple linear regression, and normative change was calculated for participants with repeated measures by subtracting their lowest ratio from their highest ratio. Results: Mean (SD) interarm, interleg, dominant arm-to-leg, and nondominant arm-to-leg ratios were 0.987 (0.067), 1.005 (0.072), 1.129 (0.160), and 1.165 (0.174) for ECF ratios; and 0.957 (0.188), 1.024 (0.183), 1.194 (0.453), and 1.117(0.367) forECF/ICFratios, respectively. Arm-to-leg ratios were significantly affected by sex, age, and body mass index. Mean normative change ranged from 7.2% to 14.7% for ECF ratios and from 14.7% to 67.1% for ECF/ICF ratios.

Conclusion: These findings provide the necessary platform for extending bioimpedance-based screening beyond unilateral lymphedema.

Main findings

  • Data from three cross-sectional studies, designated A (n=486), B (n=62), and C (n=230), and two prospective repeated-measures studies, D (n=33) and E (n=87), were pooled for this study. All five studies were comparable, including only consenting participants who were healthy by self-report and excluding those with a history of lymphedema, cancer, surgery, or radiotherapy to the regional lymph nodes.
  • To advance measurement precision, this study provides novel normative data for arm-to-leg ratios of ECF (R0) and ECF/ICF (Ri:R0) for comparison purposes. A key finding of this study was that interlimb ratios of Ri:R0 showed greater variation between subjects (up to 39.7%) compared with interlimb ratios of R0 (up to 14.9%).
  • The between-subject variation for arm-to-leg ratios was twice that for ratios between arms or between legs. Variation in arm-to-leg ratios was partially explained by the influences of sex, age, and body mass index, suggesting the need for stratified reference ranges for arm-to-leg ratios.