Joe Mabel, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons

Vital capacity is a measure of how much air a person can expel from their lungs while breathing. It is a prevalent and important measure of lung function. Tests to determine someone’s vital capacity are an important part of measuring and diagnosing many conditions that affect the respiratory system, including ALS.

How Vital Capacity is Measured

Vital capacity is measured through a type of test known as spirometry. While there are several different methods for conducting a spirometry test, they all involve breathing into a tube connected to a device called a spirometer. The spirometer measures the amount of air being released, the force with which the air is being pushed out, and other factors. In most cases, someone asked to take a spirometry test will wear a clip over their nose, take a deep breath to fill up their lungs, put their mouth around the tube, and then exhale as much as they can.

Spirometry can also be a part of a larger panel of tests to evaluate someone’s overall respiratory health. A typical adult can exhale roughly between three to five liters of air from their lungs, by volume, depending on factors including their age, height, and sex. There are many respiratory conditions that can reduce the volume someone is able to exhale, including restrictive lung diseases that limit the lungs’ ability to fully expand.

Vital Capacity in ALS

In the case of neuromuscular diseases like ALS, weakening of the muscles that control breathing, such as the diaphragm, reduces the body’s ability to take in and push out air. Because ALS symptoms worsen over time, vital capacity can be a useful benchmark for tracking progression. These respiratory symptoms are particularly important to keep track of, as complications from declining pulmonary function are the leading cause of death for people with ALS. Vital capacity scores can help people with ALS and their doctors decide whether noninvasive or invasive ventilation is necessary to help with breathing.

Forced vs. Slow Vital Capacity

Spirometry tests typically focus on a specific measure of vital capacity called “forced vital capacity (FVC).” FVC represents the amount of air that can be taken in with a deep breath and expelled from the lungs with a powerful, forced breath. Forced vital capacity is found by having someone take in the largest breath they possibly can and expel all the air in their lungs as fast as possible into the spirometer tube.

FVC is the most common measure of vital capacity, but there are other alternative tests. For people with ALS, another measure that is sometimes used is Slow Vital Capacity (SVC). An SVC test is like an FVC test, beginning with a full inhale of as much air as one can breathe in. The key difference is in the exhale—rather than forcing out all the air as quickly as possible, in an SVC test, a person will let their breath out in a slow, relaxed manner, until their lungs are empty. Like FVC, this test is meant to measure the full capacity of someone’s lungs, but it is useful in conditions like ALS, where the ability to force out air quickly is limited.

FVC, SVC, Clinical Care, and Clinical Trials

At ALS clinics, both FVC and SVC tests are still regularly used at the discretion of clinical care teams as prognostic indicators—measures that help doctors learn about a patient’s current and future symptom severity and progression. When using either vital capacity test as a benchmark for ALS, the results are measured against a “predicted FVC/SVC” number and expressed as a percent. This predicted FVC/SVC represents the average expected vital capacity for a healthy person of the same height, weight, and sex. For example, if someone has an SVC of 70%, that means their SVC test results are about 70% of what would be expected of a healthy person who matches their demographics.

In most cases, studies have shown that FVC and SVC tend to be very close to each other, making them often roughly interchangeable. FVC is the more common test, both in general and for people with ALS. However, some studies have argued that, because SVC tests require less force, they are easier to perform and preferable for assessing respiratory function in ALS. Some studies have even suggested that SVC may be a more reliable measure of ALS progression in certain cases, such as in people with bulbar-onset ALS.

FVC and SVC are also commonly used as inclusion and/or exclusion criteria for clinical trials. Many trials will set a minimum percentage for SVC or FVC, sometimes specifying one particular test, or allowing for both. For example, if a trial features an SVC of 70% as an inclusion criterion, only people who have received an SVC score higher than 70% of their predicted value at the time of enrollment may participate.

Using prognostic indicators like SVC and FVC in clinical trials allows researchers to make sure that potential participants have not progressed to the point where they are unlikely to receive benefits from a treatment. Researchers have also found that, in some cases, changes in FVC and SVC can be a useful outcome measure or benchmark to measure the success of a treatment in clinical trials.

Searching for More Tools for Measuring ALS Progression

Tools like SVC/FVC are very important for both clinicians caring for people with ALS and researchers conducting clinical trials to find new treatments. Being able to accurately assess a person’s respiratory symptoms is essential to determining if a potential treatment is having an effect in a study. Unfortunately, many other symptoms of ALS are much more difficult to measure objectively.

Instead, clinicians and researchers must currently rely on subjective measures like the ALSFRS-r survey. To address this issue, ALS researchers are working to discover new biomarkers for ALS. Biomarker are measurable biological “fingerprints,” like blood glucose for diabetes or LDL cholesterol for heart disease, that can measure and predict disease severity and prognosis.

At the ALS Therapy Development Institute (ALS TDI), we are working through our ALS Research Collaborative (ARC) program to partner with people with ALS all over the world to collect data and to search for potential biomarkers.

These efforts include our first-in-kind In-Home Blood Collection program, which allows ARC participants to contribute regular blood samples by mail without leaving their homes. By studying these samples over time, we aim to identify more potential blood-based biomarkers that could correlate with disease progression. In 2022, ALS TDI received a grant from the Department of Defense (DOD) to fund an expansion of this program, along with more advanced sample testing with the potential to reveal new protein biomarkers of ALS.

In addition to using biological samples, ARC researchers are working to use data to create digital biomarkers for tracking ALS progression. Some participants in the program are provided with digital accelerometers to be worn on the arms and legs to generate movement data and asked to periodically record voice messages to keep track of vocal function.

 In 2022, ALS TDI and our research partners at Google announced a new, machine-learning-powered tool that can accurately predict a person’s ALSFRS-r by analyzing these voice recordings. A second paper, published in 2023, in partnership with researchers from Massachusetts General Hospital, used data from ARC to support the potential of accelerometers worn throughout the day as a measure of progression.

Anyone diagnosed with ALS and asymptomatic carriers of ALS-related genetic mutations can participate in the ARC study and help contribute to this important research.

To learn more about the ALS Research Collaborative, click here.

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