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Estimating acceleration time point of respiratory decline in ALS patients: A novel metric

      Highlights

      • Acceleration timing of respiratory decline in ALS was introduced as a novel metric.
      • Logistic curve fitted well with the time-serial decline in %VC, estimating acceleration.
      • The acceleration timing strongly correlated with respiratory/nutritional support timing.
      • The acceleration time-point was at which %VC is becoming 0.789 times of maximum %VC.
      • This new metric may be of help in the management for earlier stage ALS.

      Abstract

      Objective

      We aimed to derive and assess a novel metric for respiratory decline: the timing of acceleration of respiratory functional decline during the course of the disease in patients with amyotrophic lateral sclerosis (ALS).

      Methods

      In this single-center retrospective study, we reviewed consecutive definite/probable ALS patients, diagnosed and followed up at our hospital. We recorded serial slow vital capacity (percentage of predicted slow vital capacity; %VC) since diagnosis for all patients. These serial %VC data were fitted with logistic function of the time since diagnosis, and ‘acceleration point’ was calculated as the week in which the second derivative of the fitted logistic function had the minimum value.

      Results

      We included 62 patients with ALS, whose serial %VC data had been recorded for a median of 8 times over a median of 94.3 weeks. The calculated acceleration time-point was the time-point at which the %VC is becoming 0.789 times of maximum %VC, and had a strong association with the period since diagnosis to the administration of nutritional/respiratory support (p < 0.001). Bulbar-type ALS or lower Body Mass Index at diagnosis, both are well-known ALS prognostic factors, were also associated with more rapid arrival of the acceleration time-point.

      Conclusions

      We introduced the time-point of acceleration in the vital capacity decline during disease progression as a novel metric for ALS respiratory decline. Although we could not build a practically-available clinical model that directly predicts acceleration time-point due to the limited sample size, our metric may be used as one of the helpful indicators in the management during earlier disease course of ALS, such as to be careful for the potentially approaching acceleration time-point when the %VC is decreasing to approximately 0.789 times of initial %VC.

      Keywords

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