■呼吸肌功能不足是SMA自然史中死亡的最重要原因。因此,通过疾病改善疗法(DMT)改善或稳定呼吸功能是一个非常重要的问题。
■我们使用强制肺活量(FVC)检查了42例成年SMA患者的呼吸功能(2SMA1型,15SMA2型,24SMA3型,1SMA4型,中位年龄37岁,范围17-61年)接受nusinersen治疗的中位数为22.1个月(范围2.1至46.7个月)。使用混合效应线性回归模型评估FVC的变化。
■SMA类型1之间的基线FVC差异显着(4.0,8.0%),2(中位数为22.0%,IQR18.0-44.0),3(中位数为81.0%,IQR67.0-90.8)和,分别,4型(84.0%)患者反映了基于成年期SMA类型的呼吸损害的异质性(p<0.0001)。FVC在随访期间保持稳定(平均值-0.047,95%CI-0.115至0.020,p=0.17);亚组分析显示,2型患者FVC升高(平均0.144,95%CI0.086~0.202,p<0.0001),3/4型患者FVC降低(-0.142,95%CI-0.239~-0.044,p=0.005).
■在2型SMA患者中观察到的FVC的改善可以看作是与自发过程中通常看到的进行性下降不同的治疗反应。对于在基线接近正常肺活量的SMA3/4型患者,由于天花板效应,FVC作为结果参数的用途可能有限。
UNASSIGNED: Insufficiency of respiratory muscles is the most important reason for mortality in the natural history of SMA. Thus, improvement or stabilization of respiratory function by disease-modifying therapies (DMT) is a very important issue.
UNASSIGNED: We examined respiratory function using forced vital capacity (FVC) in 42 adult SMA patients (2 SMA type 1, 15 SMA type 2, 24 SMA type 3, 1 SMA type 4, median age 37 years, range 17-61 years) treated with nusinersen for a median of 22.1 months (range 2.1 to 46.7 months). Change in FVC was assessed using mixed effects linear regression models.
UNASSIGNED: Baseline FVC differed significantly between SMA type 1 (4.0, 8.0%), 2 (median 22.0%, IQR 18.0-44.0), 3 (median 81.0%, IQR 67.0-90.8) and, respectively, type 4 (84.0%) patients reflecting the heterogeneity of respiratory impairment based on the SMA type in adulthood (p < 0.0001). FVC remained stable during follow-up (mean -0.047, 95% CI -0.115 to 0.020, p = 0.17); however, subgroup analysis showed an increase in FVC of type 2 patients (mean 0.144, 95% CI 0.086 to 0.202, p < 0.0001) and a decrease in FVC of type 3/4 patients (-0.142, 95% CI -0.239 to -0.044, p = 0.005).
UNASSIGNED: The observed improvement in FVC in patients with SMA type 2 can be seen as a therapeutic response differing from the progressive decline typically seen in the spontaneous course. For SMA type 3/4 patients approaching normal spirometry at baseline, FVC may only be of limited use as an outcome parameter due to ceiling effects.