6MWT With LOPD Patients May Depend Most on Age, Walker Use
Age and the use of an assistive device like a walker may tell how well a patient with late-onset Pompe disease will do in a six-minute walk test (6MWT), a small study suggests.
The 6MWT is considered a gold standard for determining, through difficulties in walking, the severity of muscle weakness caused by Pompe disease. The tool is used in clinical trials to assess a potential treatment’s effectiveness.
Repeat testing can lead to variations in 6MWT performance, however, for reasons that can range from changes in heart rate to fatigue and even “poor” test instructions, the researchers noted in setting out to “gain better understanding of the determinants of 6MWT performance” in people with late-onset Pompe disease (LOPD).
“Although the 6MWT score is a simple tool, the test’s determinants needed to be better defined for potential use in evaluating whether or not a treatment is effective,” the team wrote.
The study, “Factors impacting performance on the 6-minute walk test by people with late-onset Pompe disease,” was published in the journal Muscle & Nerve.
With Pompe, a mutation in the GAA gene affects the enzyme, acid alpha-glucosidase, that breaks down a large sugar molecule called glycogen. When the enzyme is not produced correctly or when it’s lacking, glycogen builds to toxic levels inside cells, especially those in muscles.
Late-onset Pompe disease patients, with onset in childhood or adulthood, often experience muscle weakness that can make it hard to walk, and they may develop breathing problems and, possibly, cardiac issues.
A team of researchers in France evaluated the 6MWT in 15 LOPD patients (nine women and six men; median age of 57) with a mean disease duration of 16 years, who were being treated every two weeks at their Lille clinic with the enzyme replacement therapy Myozyme (alglucosidade alfa; sold in the U.S. as Lumizyme).
As part of that treatment, all underwent a biannual evaluation that involved the 6MWT given at least twice, and were known to be able to do this test. Four of the 15 patients used a walker, and nine required nighttime ventilation support to help with breathing.
Researchers looked for a link between how well the patients performed on the 6MWT and their motor, lung, and heart function, compared with a control group of eight healthy individuals — four women and four men with a median age of 46.
All were asked to walk as far as possible along a 150-meter (492 feet) corridor for six minutes, with assistive devices used as needed. Patients walked more slowly and took smaller steps than did controls, and they covered a shorter mean distance (364 meters vs. 618 meters), the researchers noted. However, both groups showed a similar degree of fatigue.
Analyzing for factors that best explained variation in 6MWT performance, the team found that a person’s age and the use of an assistive device for walking — “which was highly correlated with … muscle weakness” — explained 85.5% of the variation.
They also found that cardiorespiratory changes, or how the heart and the lungs adapt during a walk, can predict variation in 6MWT performance.
In analyses of heart and lung function, the researchers expected that “the pCO2 [partial pressure of carbon dioxide, a measure of carbon dioxide within arterial or venous blood] would increase during the 6MWT.” But they observed a decrease in pCO2 in five patients and six controls as they recovered from the walk, indicating an increase in ventilation.
“Patients hyperventilated and displayed a decrease in their pCO2,” they wrote, noting hyperventilation explained why “the best respiratory parameter” in their analysis was “baseline pCO2” and not that measured during or soon after exercise.
Indeed, pCO2 measured prior to a 6MWT along with the heart rate recovery after one minute explained 42.2% of test variation, they reported. Heart rate recovery, or HRR, refers to the decrease in the speed at which the heart beats after exercise.
“Our results highlighted the importance of respiratory and cardiac adaptation during exercise (along with motor ability),” the researchers wrote.
A study limitation was its relatively small size and larger studies are needed, the researchers noted.
“Although the 6MWT is a simple, useful, functional test, the result must be interpreted in the light of other variables: (i) age and the use of an assistive device …, (ii) respiratory adaptation during the test, and (iii) HRR,” the team concluded.
“Although levels of fatigue and motivation can modify performance, the 6MWT result can be trusted if other variables (such as HRR or respiratory variables) change,” they added, with age and assistive device use being the “best clinical predictors of 6MWT performance.”