Introduction Nusinersen is used in spinal muscular atrophy (SMA) to improve peripheral muscle function; however, respiratory effects are largely unknown. Aim To assess the effects of nusinersen on respiratory function in paediatric SMA during first year of treatment. Methods A prospective observational study in paediatric patients with SMA who began receiving nusinersen in Queensland, Australia, from June 2018 to December 2019. Outcomes assessed were the age-appropriate respiratory investigations: spirometry, oscillometry, sniff nasal inspiratory pressure, mean inspiratory pressure, mean expiratory pressure, lung clearance index, as well as polysomnography (PSG) and muscle function testing. Lung function was collected retrospectively for up to 2 years prior to nusinersen initiation. Change in lung function was assessed using mixed effects linear regression models, while PSG and muscle function were compared using the Wilcoxon signed-rank test. Results Twenty-eight patients (15 male, aged 0.08–18.58 years) were enrolled: type 1 (n=7); type 2 (n=12); type 3 (n=9). The annual rate of decline in FVC z-score prior to nusinersen initiation was −0.58 (95% CI −0.75 to −0.41), and post initiation was −0.25 (95% CI −0.46 to −0.03), with a significant difference in rate of decline (0.33 (95% CI 0.02 to 0.66) (p=0.04)). Most lung function measures were largely unchanged in the year post nusinersen initiation. The total Apnoea–Hypopnoea Index (AHI) was reduced from a median of 5.5 events/hour (IQR 2.1–10.1) at initiation to 2.7 events/hour (IQR 0.7–5.3) after 1 year (p=0.02). All SMA type 1% and 75% of SMA types 2 and 3 had pre-defined peripheral muscle response to nusinersen. Conclusion The first year of nusinersen treatment saw reduced lung function decline (especially in type 2) and improvement in AHI.

Respiratory effects of nusinersen in Spinal Muscular Atrophy (SMA) are largely unknown. Aim: To assess change in respiratory function in pediatric SMA in year 1 of nusinersen treatment & compare to pre-treatment decline rate. Methods: 12-month prospective study of all childhood SMA type 1-3 in Queensland, Australia from 2018. Peripheral muscle strength tests performed prior to & 4 occassions during study with age appropriate respiratory tests attained each visit. Full diagnostic Polysomnography conducted initially & study completion. Lung function 2 years prior to study collected retrospectively. Rates of lung function decline compared prior to & following comencement of nusinersen. Comparisons made between PSG pre & post 12 months treatment. Muscle strength responders & non-responders compared for respiratory parameter change. 31 children included (18 males, 0.25-18.8 years old), 19% SMA type 1, 52% type 2 & 29% type 3. Annual rate decline of Forced Vital Capacity (FVC) z-score reduced for SMA type 2 (p=0.009) and type 3 SMA (p=0.3). Mean total apnoea-hypopnoea index reduced in type 1 [12.3 events/hour to 3.7], type 2 [4.5 (SD 3.0 95% CI 1.8-7.3) to 2.9 (SD 3.0 CI 0.1-5.6) p=0.1] and type 3 [5.3 (SD 2.2 95% CI0.14-10.8) to 2.5 (SD 19.98 95%CI 4.34) p=0.4]. No change in FVC z-score between responders and non-responders was noted (FVC z-score 0.5 p=0.5 95%CI -1.2-2.1 r<0.001 and 0.1 p=0.9 95%CI -2.4-2.6 r=0.01 respectively). Conclusion: Nusinersen stabilises lung function, halts progressive decline seen before treatment in type 2 and 3 SMA. Lung function stability seen even in those without peripheral muscle strength response. Improvements in sleep disordered breathing seen in type 1-3.

Background Spinal muscular atrophy (SMA) causes progressive respiratory muscle weakness but respiratory function (RF) in those using noninvasive ventilation (NIV) is not well described. Objective To describe RF in childhood SMA and assess differences between those using and not using NIV. Methods A cross-sectional study of childhood SMA assessed polysomnography (PSG), spirometry, forced oscillation technique (FOT), lung clearance index (LCI), sniff nasal inspiratory pressures, peak cough flow, maximal inspiratory and expiratory pressure, and NIV use and indication. Results Twenty-five children (median age [interquartile range], 8.96 [5.63] years; 10 F) with SMA 1 (n = 3), 2 (n = 15), and 3 (n = 7) were recruited. Spirometry and FOT testing was feasible in children as young as 3 years. Ten (40%) required NIV, 5 for sleep-disordered breathing (SDB), and 5 initiated during lower respiratory tract infection (LRTI). Children requiring NIV were older (median, 10.52 vs 5.67 years; P < .02) with more abnormal forced vital capacity (FVC) z-score (-5.70 vs -1.39, P < .02), Rsr8 z-score (1.97 vs 0.50, P = .04), and LCI (8.84 vs 7.34, P = .01). Two had normal RF and SDB. For FVC z-score less than -2.5 and LCI greater than 7.5, the odds ratio for NIV was 10.70 (95% confidence interval [CI], 1.39-82.03) and 2 (95% CI, 0.40-10.31), respectively. All children with LCI greater than 8 used NIV. FVC z-score and LCI are associated with maximum transcutaneous carbon dioxide on PSG (r = 0.43, P < .001). Conclusion NIV is common in SMA. Normal RF does not exclude SDB. Children with more abnormal FVC and LCI should be considered at risk of starting NIV during/following an LRTI.