Retrospective analysis suggests that slow vital capacity may have prognostic value when it comes to amyotrophic lateral sclerosis.
Jinsy Andrews, MD, MSc
Slow vital capacity (SVC), the percentage measurement of respiratory function decline, may have prognostic value when it comes to patients with amyotrophic lateral sclerosis (ALS), according to new study data.
Led by Jinsy A. Andrews, MD, MSc, the director of neuromuscular clinical trials at Columbia University, the retrospective analysis examined the relationship between SVC and major clinical events - including death - in 893 patients with ALS. The investigators use data from the EMPOWER and BENEFIT-ALS trials as well as the PRO-ACT trial database.
“The biggest takeaway for a neurologist is that the rate of decline in respiratory function, as measured by SVC, is associated with clinical events such as respiratory failure, tracheostomy or death,” Andrews told MD Magazine. “In a disease that is clinically diagnosed with variable presentation and variable rates of disease progression, the rate of decline in SVC is an objective measure that can help guide management of patients with ALS."
The analysis revealed that from baseline (mean SVC, 90.5% [Standard Deviation, 17.1%]), the average patient in EMPOWER (n = 456) declined 2.7 percentage points per month at the 1.5-year follow-up. Patients in the BENEFIT-ALS study (n = 210) and PRO-ACT database (n = 227) experienced an average decline of 2.73 and 2.90 percentage points per month, respectively.
Each group’s decline was included in a Cox proportional hazards regression model to evaluate the time to clinically meaningful ALS events, such as tracheostomy, respiratory insufficiency, dyspnea, orthopnea, or death. Results of the model showed that slowing SVC’s rate of decline to 1.5 percentage points per month reduced the risk of respiratory insufficiency by 22%, the risk of tracheostomy by 23%, and death by 23% (P <.001).
“This suggests that specifically, the rate of decline in SVC may predict these events,” Andrews said. “Despite the heterogeneous presentation and progression of patients with ALS, they all ultimately experience respiratory symptoms and die from typically die from respiratory failure. Additionally, vital capacity is important in clinical management to determine the need for non-invasive ventilation and determine the timing of recommendations for feeding tube and operative risks.”
Andrews and colleagues also examined SVC’s relationship to the questions in the respiratory subdomain of the ALS Functional Rating Scale-Revised (ALSFRS-R), which the authors suggest “may not be a sensitive indicator of respiratory function in ALS.”
At baseline, 1095 patients scored ≤39 on the ALSFRS-R, compared to 1242 patients that scored >39. The higher scoring group experienced an SVC decline of 2.3 percentage points per month. A steeper decline in ALSFRS-R of 3.1 percentage points was noted in the lower-scoring group. When SVC decline was slowed to 1.5 percentage points in that group, a 19% risk reduction in ALSFRS-R events - dyspnea, orthopnea, respiratory insufficiency - was shown (P <.001).
“This information is important in the doctor-patient relationship as it provides important information about clinical disease progression and helps the doctor anticipate management needs in the future and helps the patient understand their own disease progression since there are no validated biomarkers or staging system at present for this variable but inevitably fatal disease,” Andrews said.
The study was published in JAMA Neurology.