Long-Term Variability of Distortion-Product Otoacoustic Emissions in Infants and Children and Its Relation to Pediatric Ototoxicity Monitoring.
Long-Term Variability of Distortion-Product Otoacoustic Emissions in Infants and Children and Its Relation to Pediatric Ototoxicity Monitoring.
复制标题
儿童和儿童的失真产品耳声发射及其与小儿耳毒性监测的关系的长期变化。
DOI：
10.1097/aud.0000000000000536
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Dille M
中科院分区：
文献类型：
--
作者：
Konrad-Martin D;Knight K;McMillan GP;Dreisbach LE;Nelson E;Dille M
畸变产物耳声发射（DPOAE）为与化疗相关的外毛细胞损伤提供了一种快速、无创的测量方法，是儿童耳毒性监测的关键组成部分。参照基线测量值对DPOAE水平进行连续监测是检测耳毒性损伤的一种方法。在这种情况下解读DPOAE的检测结果需要考虑测试 - 复测差异与正常变异性的关系，而儿童在这方面的数据是缺乏的。本研究旨在（1）使用常见的临床仪器和刺激参数，描述在反映儿童化疗方案的较长时间段内，不同儿童年龄和f2主频率下DPOAE水平的正常测试 - 复测变异性；（2）制定水平变化参考区间；（3）考虑在生命早期听觉系统经历成熟变化时可能出现的DPOAE水平或测量误差的任何年龄相关变化。
在初次（基线）就诊时，对38名听力正常的健康儿童（25名女性和13名男性）进行了连续的DPOAE测量，年龄从1个月到10岁不等。平均而言，在6.5个月的观察期内，儿童接受了5.2次测试。数据以DP - 图的形式收集，其中对于f2在1.4 - 10 kHz范围内测量DPOAE水平，采用固定的f2/f1比值为1.22，L1/L2的刺激水平为65/55 dB SPL。使用纵向数据的贝叶斯回归估计年龄对DPOAE水平和测量误差的影响。使用几个年龄和f2的测量均值和标准误差（SEM）来描述DPOAE测试 - 复测差异的原始分布和基于模型的分布。
本研究中儿童的DPOAE测试 - 复测差异处于先前在成人中观察到的较高水平，这反映在相关的变化参考区间中。此外，尽管我们观察到DPOAE水平在儿童个体之间存在显著差异，但年龄相关变化的模式在儿童之间高度一致。在较宽的f2范围内，从1个月到13个月大时，DPOAE水平下降3 - 4 dB，随后每年下降幅度更缓，小于1 dB。6 kHz的f2在早期快速成熟阶段下降幅度最小。DPOAE测量误差随年龄变化相当稳定。在大多数f2处为3 - 4 dB，在1.5、8和10 kHz处更大（表明可靠性较差）。
DPOAE水平随儿童年龄增长而下降，在生命的第一年变化最大。婴儿期的成熟效应以及在非常低和高f2处较大的测量误差影响儿童的测试 - 复测变异性。6 kHz的f2显示出最小的成熟变化和测量误差，这表明它可能是儿童患者耳毒性监测的最佳监测频率。一旦用当地制定的正常数据进行验证，本文提供的参考区间可用于确定使用DPOAE进行连续监测的筛查失败标准。采用最先进的校准技术可能会降低变异性，从而允许制定更灵敏的筛查失败标准。
Distortion product otoacoustic emissions (DPOAEs) provide a rapid, noninvasive measure of outer hair cell damage associated with chemotherapy, and are a key component of pediatric ototoxicity monitoring. Serial monitoring of DPOAE levels in reference to baseline measures is one method for detecting ototoxic damage. Interpreting DPOAE findings in this context requires that test retest differences be considered in relation to normal variability, data which are lacking in children. This study sought to (1) characterize normal test-retest variability in DPOAE level over the long time periods reflective of pediatric chemotherapy regimens for a variety of childhood ages and f2 primary frequencies using common clinical instrumentation and stimulus parameters; (2) develop level-shift reference intervals; and (3) account for any age-related change in DPOAE level or measurement error that may occur as the auditory system undergoes maturational change early in life. Serial DPOAE measurements were obtained in 38 healthy children (25 females and 13 males) with normal hearing and ranging in age from one month to 10 years at the initial (baseline) visit. On average, children were tested 5.2 times over an observation period of 6.5 months. Data were collected in the form of DP-grams in which DPOAE level was measured for f2 ranging from 1.4–10 kHz, using a fixed f2/f1 ratio of 1.22 and stimulus level of 65/55 dB SPL for L1/L2. Age effects on DPOAE level and measurement error were estimated using Bayesian regression of the longitudinal data. The raw and model based distribution of DPOAE test-retest differences were characterized using means and standard error of the measurement (SEM) for several ages and f2s. DPOAE test-retest differences for the children in this study are at the high end of those previously observed in adults, as reflected in the associated shift reference intervals. Further, although we observe substantial child-specific variation in DPOAE level, the pattern of age related changes is highly consistent across children. Across a wide range of f2s, DPOAE level decreases by 3–4 dB from 1 to 13 months of age followed by a more gradual decline of < 1 dB/year. An f2 of 6 kHz shows the smallest decrease during the early rapid maturation period. DPOAE measurement error is fairly constant with age. It is 3–4 dB at most f2’s and is greater (indicating poorer reliability) at 1.5, 8 and 10 kHz. DPOAE level decreases with childhood age, with the greatest changes observed in the first year of life. Maturational effects during infancy, and greater measurement error at very low and high f2’s impact test-retest variability in children. An f2 of 6 kHz shows minimal maturation and measurement error, suggesting it may be an optimal sentinel frequency for ototoxicity monitoring in pediatric patients. Once validated with locally-developed normative data, reference intervals provided herein could be used to determine screen fail criteria for serial monitoring using DPOAEs. Employing state-of-the-art calibration techniques might reduce variability, allowing for more sensitive screen fail criteria.