Natural history of lung function in spinal muscular atrophy
Natural history of lung function in spinal muscular atrophy
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DOI：
10.1186/s13023-020-01367-y
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发表时间：
2020-04-10
影响因子：
3.7
通讯作者：
van der Pol, W. Ludo
中科院分区：
文献类型：
--
作者：
Wijngaarde, Camiel A.;Veldhoen, Esther S.;van der Pol, W. Ludo
背景呼吸肌无力是脊髓性肌萎缩症（SMA）的重要特征。进行性肺功能下降是患者死亡和发病的最重要原因。然而，SMA肺功能的自然史尚未得到详细研究。结果：我们分析了170例SMA 1c-4型初治患者的2098项肺功能测量结果，年龄4 - 74岁。所有患者均参与正在进行的基于人群的患病率队列研究。我们测量了1秒用力呼气量（FEV1）、用力肺活量（FVC）和肺活量（VC）。使用线性混合效应和非线性模型分析肺功能的纵向模式。此外，我们还评估了姿势对FEV 1和FVC测试结果的影响。在早发性SMA类型（1c-3a）中，我们观察到肺功能在年轻时进行性下降，在成年期相对稳定。在病情更严重的患者中，估计的基线值显著更低：1c型SMA的%FEV1范围为42%至3b型SMA的100%，%FVC为50至109%，%VC为44至96%。SMA类型之间的平均年下降率也存在显著差异，FEV1的范围为-0.1%至-1.4%，FVC为-0.2%至-1.4%，VC为+0.2%至-1.7%。与SMA 1c-3a型相比，我们发现迟发型SMA 3b和4型在整个生命中的所有结局均正常，尽管有一些例外，并且基于有限的可用数据。最后，我们发现在坐位或仰卧位测量的FVC或FEV1值没有重要差异。结论：我们的数据说明了SMA患者肺功能的纵向过程，其特征是儿童期进行性下降，成年早期稳定。数据不支持在坐位和仰卧位测量FEV1或FVC的额外获益。这些数据可作为临床试验中评估长期结局的参考。
Background Respiratory muscle weakness is an important feature of spinal muscular atrophy (SMA). Progressive lung function decline is the most important cause of mortality and morbidity in patients. The natural history of lung function in SMA has, however, not been studied in much detail. Results We analysed 2098 measurements of lung function from 170 treatment-naive patients with SMA types 1c-4, aged 4-74 years. All patients are participating in an ongoing population-based prevalence cohort study. We measured Forced Expiratory Volume in 1 s (FEV1), Forced Vital Capacity (FVC), and Vital Capacity (VC). Longitudinal patterns of lung function were analysed using linear mixed-effects and non-linear models. Additionally, we also assessed postural effects on results of FEV1 and FVC tests. In early-onset SMA types (1c-3a), we observed a progressive decline of lung function at younger ages with relative stabilisation during adulthood. Estimated baseline values were significantly lower in more severely affected patients: %FEV1 ranged from 42% in SMA type 1c to 100% in type 3b, %FVC 50 to 109%, and %VC 44 to 96%. Average annual decline rates also differed significantly between SMA types, ranging from - 0.1% to - 1.4% for FEV1, - 0.2% to - 1.4% for FVC, and + 0.2% to - 1.7% for VC. In contrast to SMA types 1c-3a, we found normal values for all outcomes in later-onset SMA types 3b and 4 throughout life, although with some exceptions and based on limited available data. Finally, we found no important differences in FVC or FEV1 values measured in either sitting or supine position. Conclusions Our data illustrate the longitudinal course of lung function in patients with SMA, which is characterised by a progressive decline in childhood and stabilisation in early adulthood. The data do not support an additional benefit of measuring FEV1 or FVC in both sitting and supine position. These data may serve as a reference to assess longer-term outcomes in clinical trials.