With clear differences at baseline and subsequent declines seen in a linear pattern, the researchers suggested peak expiratory flow may be a suitable outcome measure for longitudinal assessment of respiratory muscle strength in these patients.
Using natural history data to map the longitudinal course of respiratory muscle strength among patients, the researchers were also able to determine which respiratory measure should be used for longer-term follow up of patients with SMA, who face morbidity and mortality due to respiratory complications.
“Improved insights into the natural history of respiratory muscle strength could guide therapeutic management, improve timing of supportive care, and facilitate its use as an outcome measure for longer-term follow-up of patients or treatment efficacy assessments,” explained the researchers.
“Tests of respiratory muscle strength may detect respiratory insufficiency earlier than more frequently used measurements of expiratory lung function [e.g. forced vital capacity (FVC)]. Longitudinal studies on the decline of respiratory muscle strength have been performed in other NMDs but not in SMA,” they added.
The researchers leveraged over 2000 respiratory measurements—peak expiratory flow (PEF), maximal expiratory and inspiratory pressure (PEmax and PImax), Sniff Nasal inspiratory pressure (SNIP), and peak cough flow—from 80 untreated patients with SMA, which consistently showed poorer outcomes among patients with more severe phenotypes of SMA. Patients included those with varying SMA phenotypes and ages (range of 4.1 to 66.6 years).
Measurements showed that at early ages, PEF varied significantly based on SMA phenotype (type 1c, 49%; type 2a, 73%; type 2b, 87%; type 3a, 96%). Over time, there was an observed linear decline (1%-2%/year) in PEF across most phenotypes and declines did not differ significantly based on phenotype. This finding suggests phenotypes are primarily separated by differences at baseline or very early in life.
With clear differences at baseline and subsequent declines in a linear pattern, the researchers suggested that PEF may be a suitable outcome measure for longitudinal measuring of respiratory muscle strength in these patients.
Over time, both and PEmax and PImax significantly dropped among patients, nearly all of whom had abnormally low PEmax values. Notably, while previous studies have indicated that patients with SMA type 3a have normal lung volumes until early adulthood, the current findings showed low PEmax in these patients beginning at an early age.
“PEmax may be the most suitable outcome of these two, as expiratory muscle function is predominantly affected in patients with SMA,” wrote the researchers. “Interestingly, PEmax was low in patients with SMA type 3a from early ages on, whilst we have previously shown that lung volumes in these patients remain normal at least until (early) adulthood. Based on these data, we believe PEmax is a sensitive screening parameter to detect respiratory muscle weakness in SMA patients,” they said.
Similar to PEmax and PImax, SNIP— suggested as an alternative or complement to PImax—was abnormally low (i.e. below below 75 cmH2O) in patients included in the study, although this was more prominent in patients with more severe phenotypes.
Veldhoen ES, Wijngaarde CA, Hulzebos EHJ, et al. Natural history of respiratory muscle strength in spinal muscular atrophy: a prospective national cohort study. Orphanet J Rare Dis. Published online February 21, 2022. doi: 10.1186/s13023-022-02227-7