Reply to Chacko <i>et al.</i>: Limited Assessment of Respiratory Muscle Response to Nusinersen Treatment in Infants with Spinal Muscular Atrophy
Authors: Antonella LoMauro, Chiara Mastella, Katia Alberti, Riccardo Masson, Andrea Aliverti, Giovanni Baranello
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Optoelectric plethysmography is a novel and interesting method of assessing breathing patterns and thoracoabdominal paradox in children with spinal muscular atrophy (SMA).LoMauro and colleagues should be commended for their efforts to quantify breathing parameters in this group of children (1).Respiratory assessment of infants with SMA is important and necessary to better understand the effects of treatments on respiratory muscle strength and respiratory function (2).Although LoMauro and colleagues did show a reduction in thoracoabdominal paradox in patients with SMA type 1C treated with nusinersen compared with untreated patients with type 1C, the patient groups they compared may not be equivalent.The treated group had higher SMN (survival motor neuron) copy numbers, which is associated with better outcomes and a milder clinical course.Patients in the treated group were significantly older than those in the untreated group, with treated patients with type 1C being the oldest of all.It is difficult to distinguish the effects of disease treatment from those of growth and development in the absence of appropriate reference data, especially considering that chest wall compliance and thoracoabdominal paradox decrease with age.Despite these differences between the patient groups, there is little doubt about the potential value of optoelectric plethysmography for providing objective outcome measures in clinical or epidemiological research studies involving infants with SMA.However, it is generally agreed that no single lung function test will ever provide the answer and that a combination of tests is required.Other respiratory assessment tools are available for children in this age group, including the widely available thoracic and abdominal effort respiratory impedance plethysmography bands, which are frequently incorporated into polysomnography recordings and record respiratory rate and thoracoabdominal paradox.It would be very interesting to compare these two methods of assessment in young children with SMA for use as clinical trial outcomes.In addition, oscillometry in children with SMA has been shown to provide valuable information and may be useful for assessing response to therapeutic interventions such as disease-modifying agents, including nusinersen (3).One of the dangers of publishing incomplete data on respiratory outcomes in young patients with SMA is the potential risk that medical insurance companies or funding bodies will use these data to deny reimbursement for or access to treatment with a potentially life-saving medication.Thus, although LoMauro and colleagues have added valuable information regarding the respiratory effects of nusinersen in infants with SMA, we caution against concluding that types 1A and 1B did not show a treatment response based on optoelectric plethysmography alone.Major gaps in our knowledge and understanding of treatment response in SMA remain.