Measures of Lung Health Help to Predict Likely Outcomes in ALS Patients, Study Suggests

Measuring lung function can help to predict overall disease progression in people with amyotrophic lateral sclerosis (ALS), a study suggests.

“Classifying Amyotrophic Lateral Sclerosis Patients by Changes in Forced Vital Capacity: A Group-Based Trajectory Analysis” was published in the American Journal of Respiratory and Critical Care Medicine.

Symptoms of ALS differ among people; as such, there is a need for ways that help to tell what a given patient’s prognosis might be so that optimal care can be given. Lung involvement can be a serious complication in ALS, so the scientists behind this study wondered if assessing lung health directly might be helpful in predicting a patient’s likely clinical outcomes.

“Given the progressive nature of ALS, early discrimination of separate phenotypes of respiratory muscle decline would prove invaluable for improving precision interventions and informing clinical trial design,” the researchers wrote.

Specifically, they were interested in changes in forced vital capacity (FVC), a fairly common metric of lung health that basically measures the amount of air a person can exhale in a given amount of time. Low FVC scores or those that decline over time are considered to be a sign of lung damage.

To begin, the researchers recruited 837 ALS patients at their center in Philadelphia, whose first visits were between 2006 and 2015. Participants were 55% male and 83% white, with an average age of 63. They were followed for a median of a year and a half, with FVC measurements taken regularly.

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Researchers then looked at trends in FVC change, and divided participants into three groups.

The first, termed the “Stable Low” group, was the largest, comprising 47% of the cohort. These individual showed a comparatively low FVC at diagnosis that remained low over the course of follow-up.

The second or “Rapid Progressor” group covered 39% of participants. These patients had a higher FVC at diagnosis, but this quickly decreased over the course of their disease.

“Slow Progressor” was the last group, making up 14% of the cohort; these people had a relatively normal FVC at diagnosis with little decline over time, meaning their lungs could empty about 80% of their volume in a number of seconds.

Significant differences in patient characteristics existed across these groups. For example, people in the Stable Low group were more likely to be older at diagnosis, to have bulbar onset disease (affecting muscles of the head and neck, making speech and swallowing difficult), and to have lower scores on the ALS Functional Rating Scale-Revised (ALSFRS-R), a measure of changes in functions like walking, swallowing or dressing oneself. In contrast, those in the Slow Progressors group were more likely to have limb-onset disease, higher ALSFRS-R scores, and better survival.

The researchers did note that bulbar weakness can interfere with FVC measurements; as such, they also did a separate analysis that excluded patients with bulbar symptoms. They found similar results, although these data were not included in the published paper.

The researchers then did a confirmatory analysis using data collected in more than 20 clinical trials, comprising information on 7,461 people (average age 55, 62% male, 95% white).

These patients were divided into the same three categories, and although the distribution was slightly different (23% Stable Low, 52% Rapid Progressor, and 25% Slow Progressor), clinical features of the three groups were similar.

They also examined the 2,777 (37%) people in the dataset who developed lung failure, looking at the length of time between diagnosis and the development of respiratory insufficiency. In the Stable Low group, the median time was 11.4 months; for the Rapid Progressor group, it was 19.2 months; and for the Slow Progressor group, 34.0 months.

These data suggest that classifying patients based on trends in lung function, as measured by FVC, has real predictive value for determining their most likely prognosis. Future research will be needed to validate these findings.

“By further refining characteristics associated with different trajectories of respiratory function, we may tailor goals of care and respiratory interventions to provide personalized medicine for ALS,” the researchers concluded.