Study question In lymphangioleiomyomatosis, airflow obstruction and impairment of gas transfer progress at variable rates and serial lung function is recommended for disease monitoring. As these measurements are variable, recognising subjects needing treatment can be difficult. We used two prospective national cohorts to study change over time and variation in FEV1 to inform clinical decision making. Patients and methods Clinical and lung function data for 141 UK and 148 American subjects were studied. Multilevel mixed effects modelling, route mean square analysis of errors and Bland-Altman analysis were used to analyse variability in lung function over time. Results At baseline assessment, DLCO was reduced to a greater degree than FEV1. In untreated patients, FEV1 and DLCO declined at proportionately similar rates independent of initial lung function. In mechanistic target of rapamycin (mTOR) inhibitor treated patients, FEV1 stabilised but DLCO continued to decline. FEV1/DLCO per cent predicted ratio was 1.37 (0.43) at baseline and increased to 1.41 (0.50) after 42 (24) months (p=0.0002). At least five measurements were required before >70% of individuals had estimates of rate of FEV1 loss within 50 mL/year and DLCO loss within 0.1 mmol/min/kPa/year of the final values. Conclusions While FEV1 and DLCO fall proportionately in most, in early disease and during mTOR inhibitor treatment, DLCO should also be monitored as it may fall independent of FEV1. Since at least five observations over many months are required to make confident estimates of FEV1 and DLCO trajectories, new strategies are needed to measure disease activity and target early treatment appropriately. Data are available upon reasonable request. Data may be obtained from a third party and are not publicly available. UK data can be made available in an anonymised format, on request from the corresponding author on a collaborative basis for academic research. US data are available with linked, anonymised clinical information from the National Disease Research Interchange (Philadelphia, USA).

中文翻译：

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在淋巴管平滑肌瘤病中使用肺功能轨迹进行疾病监测：两个国家队列的评估

研究问题 在淋巴管平滑肌瘤病中，气流阻塞和气体传输进展的损害以不同的速度和连续的肺功能被推荐用于疾病监测。由于这些测量值是可变的，因此识别需要治疗的对象可能很困难。我们使用两个前瞻性全国队列来研究 FEV1 随时间的变化和变化，为临床决策提供信息。患者和方法 研究了 141 名英国受试者和 148 名美国受试者的临床和肺功能数据。多级混合效应建模、误差路径均方分析和 Bland-Altman 分析用于分析肺功能随时间的变异性。结果 在基线评估中，DLCO 的降低程度大于 FEV1。在未经治疗的患者中，FEV1 和 DLCO 下降比例相似，与初始肺功能无关。在雷帕霉素 (mTOR) 抑制剂治疗的患者中，FEV1 稳定但 DLCO 继续下降。FEV1/DLCO 百分比预测比率在基线时为 1.37 (0.43)，在 42 (24) 个月后增加至 1.41 (0.50) (p=0.0002)。在 >70% 的人估计 FEV1 损失率在最终值的 50 mL/年以内和 DLCO 损失率在 0.1 mmol/min/kPa/年以内之前，至少需要进行五次测量。结论 虽然 FEV1 和 DLCO 在大多数情况下成比例下降，但在早期疾病和 mTOR 抑制剂治疗期间，还应监测 DLCO，因为它的下降可能与 FEV1 无关。由于需要在多个月内至少进行五次观察才能对 FEV1 和 DLCO 轨迹做出有把握的估计，需要新的策略来衡量疾病活动并适当地针对早期治疗。可根据合理要求提供数据。数据可能从第三方获得，并且不公开。英国数据可以匿名格式提供，应通讯作者的要求，在学术研究的合作基础上。美国数据可从国家疾病研究交流中心（美国费城）获得链接的匿名临床信息。