Patterns of Lung Function Decline Likely Not Predictive of Respiratory Failure in SMA

Following the course of lung function in treatment-naïve patients, researchers found that lung function decline does not accelerate prior to mechanical ventilation.

Patterns in the decline of lung function among patients with spinal muscular atrophy (SMA) are not predictive of respiratory failure, found researchers of a new study.

Findings were published in Orphanet Journal of Rare Diseases.

Following the course of lung function in treatment-naïve patients, researchers found that lung function decline does not accelerate prior to mechanical ventilation. The findings, explained the researchers, contradict previous research detailing accelerated increase in carbon dioxide levels.

“The ability to predict the need for mechanical ventilation is important to ensure that patients will not be confronted with emergency decision regarding the start of ventilation,” described the researchers. “The current data will therefore not help to improve counseling of patients about the best timing for interventions that could prevent or treat respiratory failure, in contrast to previously described pCO2 [partial pressure of carbon dioxide] levels.”

The researchers of the study included 38 treatment-naïve patients with SMA types 1c-3a who required mechanical ventilation due to chronic respiratory failure and had available lung function test results prior to ventilation. From 385 tests, the researchers determined that patients showed a gradual decline of lung function, with no indications of accelerated deterioration.

Across the patients, there was an average annual forced vital capacity (FVC) decline of 1.75% (95% CI, 0.86%-2.66%), forced expiratory volume in 1 second (FEV1) decline of 1.72% (95% CI, 1.04%-2.40%), and peak expiratory flow (PEF) decline of 1.65% (95% CI, 0.71%-2.59%). At the time of mechanical ventilation, scores for all 3 measures were approximately 30% of predicted.

“Although baseline lung function values differed between SMA types, the annual decline rates were not significantly different between different SMA types,” wrote the researchers. “This is probably due to the relatively small patient sample, since rates of decline observed in natural history studies over longer periods of time differed between SMA types. In contrast to the other parameters, PEmax [maximum expiratory pressure] remained relatively stable but very low in the years prior to mechanical ventilation, indicating that the main loss of expiratory muscle strength occurs earlier in the disease course.”

At the time of mechanical ventilation, estimated PEmax was 35.30 (95% CI, 29.41-41.36) cmH2O, and there was an average decline of 0.03 (95% CI, −0.78 to 0.66) cmH2O/year.

Median FVC, FEV1, PEF, and PEmax were all lower in patients who electively started mechanical ventilation compared with those who could not be weaned off ventilation following surgery or a respiratory tract infection. The researchers noted that their study did not add any insight into whether early initiation of mechanical ventilation is better.

Current recommendations include a strong consensus of starting mechanical ventilation after respiratory failure or hypoventilation during sleep and less consensus on beginning ventilation before respiratory failure in nonsitters or in the case of recurrent respiratory tract infections.


Veldhoen E, Wijngaarde C, van Eijk, et al. Lung function decline preceding chronic respiratory failure in spinal muscular atrophy: a national prospective cohort study. Orphanet J Rare Dis. Published online February 23, 2023. doi:10.1186/s13023-023-02634-4

Related Videos
James Howard, MD
Related Content
© 2023 MJH Life Sciences
All rights reserved.