Supplementary figures for: Respiratory trajectories in type 2 and 3 Spinal muscular atrophy in the iSMAC cohort study

Objective. To describe the respiratory trajectories and their correlation with motor function in an international paediatric cohort of patients with type 2 and non-ambulant type 3 spinal muscular atrophy (SMA).

Methods. Eight-year retrospective observational study of patients in the iSMAc natural history study. We retrieved anthropometrics, forced vital capacity (FVC) absolute, FVC% predicted (FVC%P.), Non-Invasive ventilation (NIV) requirement. Hammersmith functional motor scale (HFMS) and Revised performance of upper limb (RULM) were correlated with respiratory function. We excluded patients in interventional clinical trials and on Nusinersen commercial therapy.

Results. There were 437 patients with SMA: 348 type 2, 89 non-ambulant type 3. Mean age at first visit was 6.9(±4.4) and 11.1(±4) years. In SMA type 2 FVC%P declined by 4.2%/year from 5 to 13 years, followed by a slower decline (1.0%/year). In type 3 FVC%P declined by 6.3%/year between 8 and 13 years, followed by a slower decline (0.9%/year). 39% SMA type 2 and 9% type 3 required NIV at median age 5.0(1.8-16.6) and 15.1(13.8-16.3) years. 84% SMA type 2 and 80% type 3 had scoliosis, 54% and 46% required surgery, which did not significantly affect respiratory decline. FVC%P positively correlated with HFMS and RULM in both subtypes.

Conclusions. In SMA type 2 and non-ambulant type 3 lung function declines differently, with a common levelling after age 13 years. Lung and motor function correlated in both subtypes. Our data further defines the milder SMA phenotypes and provides novel information to benchmark the long-term efficacy of new treatments for SMA.

研究目的 本研究旨在描述2型及非行走型3型脊髓性肌萎缩症（spinal muscular atrophy, SMA）国际儿科队列患者的呼吸轨迹，及其与运动功能的相关性。

研究方法 本研究为针对iSMAc自然病史研究中受试者的8年回顾性观察性研究。研究人员收集了受试者的人体测量学数据、绝对用力肺活量（forced vital capacity, FVC）、预测值百分比用力肺活量（FVC% predicted, FVC%P.）、无创通气（Non-Invasive ventilation, NIV）需求情况。将哈默史密斯功能运动量表（Hammersmith functional motor scale, HFMS）与修订上肢功能量表（Revised performance of upper limb, RULM）得分与呼吸功能进行相关性分析。本研究排除了参与干预性临床试验及接受诺西那生钠（Nusinersen）商业治疗的受试者。

研究结果 本研究共纳入437例SMA患者，其中2型患者348例，非行走型3型患者89例。首次就诊时的平均年龄分别为6.9(±4.4)岁与11.1(±4)岁。2型SMA患者的FVC%P在5~13岁期间以每年4.2%的速率下降，之后下降速率放缓至每年1.0%。3型SMA患者的FVC%P在8~13岁期间以每年6.3%的速率下降，之后下降速率放缓至每年0.9%。分别有39%的2型SMA患者与9%的3型SMA患者需接受NIV治疗，对应的中位启动年龄分别为5.0岁（1.8~16.6岁）与15.1岁（13.8~16.3岁）。84%的2型SMA患者与80%的3型SMA患者合并脊柱侧凸，其中54%与46%的患者需接受脊柱手术，该手术未对呼吸功能下降产生显著影响。两种亚型患者的FVC%P均与HFMS及RULM得分呈显著正相关。

研究结论 2型与非行走型3型SMA患者的肺功能下降速率存在差异，但均在13岁后进入平台期。两种亚型患者的肺功能与运动功能均存在相关性。本研究数据进一步明确了表型相对轻微的SMA亚型特征，并为评估SMA新型治疗方案的长期疗效提供了新的基准参照数据。