Efficacy and safety of salbutamol in treatment of children with later-onset spinal muscular atrophy / 浙江大学学报·医学版

OBJECTIVES@#To investigate the clinical efficacy and safety of salbutamol in the treatment of children with later-onset spinal muscular atrophy (SMA).@*METHODS@#This study is a prospective single-arm phase Ⅲ clinical study. Pediatric patients with SMA type Ⅱ and Ⅲ who visited Department of Neurology, Children's Hospital, Zhejiang University School of Medicine from December 2020 to June 2022 were enrolled. All patients were evaluated with motor function scales, pulmonary function test and drug safety before study. Patients were treated with salbutamol tablets orally, with an initial dose of 1 mg (tid). If tolerable, the dose was increased to 1.5 mg (tid) in the second week, then increased to 2 mg (tid) from the third week and maintained for 6 months. Patients were followed up at 1, 3 and 6 months of treatment.@*RESULTS@#Twenty-six patients were enrolled, including 10 boys and 16 girls. There were 16 cases of SMA type Ⅱ and 10 cases of type Ⅲ with age at treatment initiation of 5.67 (3.13, 7.02) years and disease duration of 2.54 (1.31, 4.71) years. The Hammersmith Functional Motor Scale-Expanded (HFMSE) scores were increased from 14.0 (6.5, 43.0) before treatment to 26.0 (15.0, 46.5) after treatment (Z=－4.144, P<0.01) in 25 cases. The Revised Upper Limb Module Scale scores were increased from 33.0 (25.5, 36.0) before treatment to 35.0 (31.0, 36.5) after treatment (Z=－2.214, P<0.05) in 9 cases. In 7 ambulant children with SMA type Ⅲ, the six minutes walking distance was increased by 30 (15, 52) m after a 6-month treatment (Z=－2.366, P<0.05). Compared with the baseline pulmonary functions the patients showed a significant increase in forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF) in 15 cases after treatment (all P<0.05). According to patients and caregivers subjective reporting, there were various degrees of improvement in coughing, sputum production ability and exercise endurance. No serious adverse events were observed during the study.@*CONCLUSIONS@#Short-term oral administration of salbutamol may improve motor and pulmonary functions in later-onset SMA children with good safety.

Lung function of patients with spinal muscular atrophy / 中华实用儿科临床杂志

Objective:To analyze the characteristics of lung function in patients with spinal muscular atrophy (SMA) to provide evidence for multidisciplinary management of SMA.Methods:A total of 30 patients with SMA treated in the SMA multidisciplinary clinic of the Children′s Hospital, Zhejiang University School of Medicine from July 2019 to March 2021 were enrolled, including 1 child with type I, 18 patients with type Ⅱ and 11 children with type Ⅲ.There were 17 males and 13 females; the age ranged from 4 years to 21 years and 10 months old.A retrospective study was conducted to analyze the clinical features, spinal imaging findings and lung functions of patients with different clinical types of SMA and explore the factors influencing the lung functions of patients with SMA.Pulmonary function was measured by forced expiratory flow-volume curve.Forced vital capacity (FVC), forced expiratory volume in one second (FEV 1), FEV 1/FVC and peak expiratory flow (PEF) were measured.The results were expressed as the percentage of the measured value to predicted value.The Cobb angle was measured to evaluate scoliosis. Pearson correlation analysis and multiple linear regression analysis were used to evaluate the relationship between lung function and age and Cobb angle in patients with type Ⅱ SMA. Pearson correlation analysis and univariate linear regression analysis were used to evaluate the relationship between Cobb angle and age in patients with type Ⅱ SMA. Results:Pulmonary function in 1 type I patient showed decreased FVC and FEV 1; Among 18 patients with type Ⅱ, 14 cases had abnormal lung function (77.8%): FVC decreased in 12 patients (66.7%), FEV 1 decreased in 10 patients (55.6%), PEF decreased in 12 patients (66.7%). Among 11 patients with type Ⅲ, one had decreased FVC (9.1%). FVC, FEV 1 and PEF of patients with type Ⅱ were significantly lower than those of patients with type Ⅲ [(62.4±31.8)% vs.(90.8±11.0)%, (66.3±33.3)% vs.(97.8±9.9)%, (65.3±30.1)% vs.(98.6±21.1)%, all P<0.01]. Pearson correlation analysis showed that FVC of patients with type Ⅱ SMA was correlated with age and Cobb angle ( r=-0.864, -0.865, all P<0.001), FEV 1 was correlated with age and Cobb angle ( r=-0.878, -0.863, all P<0.001), PEF was correlated with age and Cobb angle ( r=-0.831, -0.783, all P<0.001), and Cobb angle was related to age ( r=0.922, P<0.001). Multiple linear regression analysis indicated that FVC of patients with type Ⅱ SMA was linearly correlated with Cobb angle ( R2=0.748, P<0.001), FEV 1 was linearly correlated with age ( R2=0.770, P<0.001), PEF was linearly related to age ( R2=0.690, P<0.001). Univariate linear regression analysis revealed that Cobb angle of patients with type Ⅱ SMA was linearly related to age ( R2=0.851, P<0.001). Conclusions:FVC, FEV 1 and PEF may decrease in patients with SMA.The degree of lung function damage is different in different types of SMA patients.With the increase of age, Cobb angle increases and FVC, FEV 1 and PEF decrease in patients with type Ⅱ SMA.Understanding the factors influencing the pulmonary function damage in patients with SMA is conductive to carrying out individual multidisciplinary management.