In medicine, the discovery of a disease is usually followed by a period of characterizing it in clinical terms, which can help future physicians diagnose the condition and monitor its signs and symptoms. Eventually, attention turns towards finding a cure, or at least finding a way to manage the clinical manifestations of the disease as best as possible. 

Further down the road, physicians would want to be able to measure disease progression based on objective clinical outcomes. For example, for a patient with respiratory disease, subjective statements such as “I feel better/worse today” do not hold much value (although they are useful in helping physicians understand how the patient is perceiving his or her illness). What physicians want are research-based, scientific, and reproducible approaches to measuring disease outcomes. 

This is especially true when the patient suffers from conditions that cause multiple pathologies in the body, such as Pompe disease. In these cases, deterioration in one organ may very much affect another organ, or may not at all. In either case, physicians need to be able to keep track of the relative health of various systems in the body in an objective manner. 


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One of the most widely used tests to monitor motor decline in patients with Pompe disease is the 6-minute walk test (6MWT). This test has become the standard assessment to gauge functional exercise capacity for a number of diseases, especially those that relate to the cardiovascular, respiratory, and skeletomuscular systems. 

A ‘Practical and Simple’ Assessment

What is the 6MWT? In the Annals of the American Thoracic Society, Brown and Nathan wrote, “The 6MWT is a practical and simple test that provides a global measure of functional capacity. It does not distinguish between contributing elements to exercise limitation, which could include pulmonary, cardiovascular, and neuromuscular factors.”

A key advantage of this test is that it does not require the use of any special (and potentially expensive) equipment. In addition, the patient does not need any training or extensive preparation for the test. This makes it highly useful in clinical studies and practice. 

The instruction is simple: Walk as far as possible in 6 minutes. This may be done back and forth if the test is conducted in a small room. Participants are allowed to slow down or stop, but are encouraged to do their best during the 6 minutes.

Read more about Pompe disease etiology

Why 6 minutes and not 7 or 8? First, we must acknowledge that there are various motor capacity tests that are of various durations. Second, it appears that 6 minutes is the ideal timeframe for the physician to get a decent sense of the exercise capacity of a patient; too short a time and the assessment becomes worthless, too long and the patient may get breathless and tired. 

Also, once a specific duration has been established, it should not be changed arbitrarily. This is so that physicians can carry out the same test for the same duration and know that the results are reproducible if conducted anywhere else. 

Tracking Disease Progression

In Cells, Claeys and colleagues wrote about a study they conducted on the usefulness of the 6MWT as a measure of motor decline in patients with late-onset Pompe disease. The defining features of Pompe disease are progressive limb-girdle muscle weakness and respiratory insufficiency. Hence, the monitoring of motor function is key to the management of this disease. 

The 6MWT is not merely a measurement of motor decline; it also contributed to the current treatment regime of enzyme replacement therapy (ERT) coming into existence. Most clinical studies involving ERT and Pompe disease used the 6MWT as an outcome measure because researchers found it superior to other motor function assessments.

Read more about Pompe disease treatment 

In the study conducted by Claeys and colleagues on 6MWT, they discovered a significant decline in 6-minute walking distance (6MWD) after 2 years of treatment. The mean distance decreased from about 452 m to about 368 m. This is consistent with other studies that reported a decline in 6MWD after 2-3 years of treatment in patients with late-onset Pompe disease. 

The research team wrote, “A change in the mean distance in 6MWD in patients of 83.8 m (representing about 18% of the initial mean value of 451.9 m) represents a clinically meaningful change according to literature data.” 

This study further cements the usefulness of the 6MWT to track disease progression. Like Brown and Nathan, Claeys and colleagues praised the simple and elegant design of the test. It is quick, inexpensive, easy to perform, and can be used in ambulatory patients regardless of their age, sex, height, weight, skeletal issues, and motivation.

Forming a Broader Clinical Picture

Claeys et al recommended a number of other assessments that can complement the 6MWT to give physicians a more comprehensive clinical picture of the condition of their patients: 

  • Forced vital capacity 
  • Patient-reported outcome measures
  • Rasch-built Pompe-specific Activity (R-Pact) scale, which measures daily activities
  • Isometric strength measured using a dynamometer. 

The decades-long history of the 6MWT has demonstrated its enduring appeal in measuring motor outcomes in Pompe disease and other conditions. It also proves that the best testing parameters need not be expensive and burdensome; a little imagination can go a long way. Undoubtedly, the 6MWT will continue to be used in clinical studies and practice in the decades to come. 

References

Brown AW, Nathan SD. The value and application of the 6-minute-walk test in idiopathic pulmonary fibrosisAnn Am Thorac Soc. 2018;15(1):3-10. doi:10.1513/AnnalsATS.201703-244FR

Claeys KG, D’Hondt A, Fache L, Peers K, Depuydt CE. Six-minute walk distance is a useful outcome measure to detect motor decline in treated late-onset Pompe disease patientsCells. 2022;11(3):334. doi:10.3390/cells11030334