BACKGROUND
 
The six-minute walk test (6MWT) was introduced into clinical practice almost half a century ago. Gradually, it became the most widely used field exercise test in chronic respiratory disease. Despite advances in standardization,(1,2) there are some aspects of test performance and interpretation that should be carefully tempered by individual clinical judgment (Chart 1).
 

 
OVERVIEW
 
A 49-year-old woman presenting with a BMI of 34.2 kg/m2, antiphospholipid syndrome, and two episodes of submassive pulmonary embolism developed chronic thromboembolic pulmonary hypertension . The six-minute walk distance (6MWD) increased from 198 m to 336 m after administration of riociguat. Over the next 6 months, she reported a decrease in exercise tolerance: her DLCO, a ventilation-perfusion scan, and a transthoracic echocardiogram did not suggest disease progression. However, the 6MWD decreased by 72 m, i.e., approximately twice  the recently estimated minimal clinically important difference of 33 m.(3) Given the conflicting results, she was referred for right heart catheterization, which confirmed hemodynamic stability. A review of the results of the latest 6MWT showed the following: a) a pronounced increase in the body weight (BMI, 41.2 kg/m2); b) a shift from dyspnea to limiting “leg fatigue” associated with palpitations, lightheadedness, and limb paresthesia; and c) an SpO2 of 99-100% on room air. Cardiopulmonary exercise testing revealed the negative effects of obesity, physical deconditioning, and dysfunctional breathing/hyperventilation. After aggressive weight loss (BMI, 30.7 kg/m2), physical reconditioning, anxiety control, and breathing exercises, the 6MWD increased to 389 m, with marked symptom improvement.
 
The 6MWT is a self-paced test of functional walking capacity that neither provides a metric of physical performance/fitness nor gives the causes of exercise limitation.(1,2) These considerations should not prevent the reader from seeking information beyond the 6MWD. For instance, in the case reported here, a more careful consideration of the ancillary findings (obesity progression, patient symptoms, and supra normal SpO2 on room air suggesting deconditioning and hyperventilation) in light of other data indicating disease stability might have avoided a futile invasive procedure (right heart catheterization). Continuous monitoring of SpO2 improves the yield of oximetry in predicting mortality and hospitalization in patients with COPD.(4) Paradoxically, however, it can have undesirable consequences, such as early exercise interruption and slowing down at a “critically low” SpO2 that could be faced in daily life without major implications. Patients experiencing the long-term consequences of disabling dyspnea and self-restraint are less likely to walk faster after an effective intervention; that is, they “can,” but “won’t.” In fact, the test is notoriously more sensitive to interventions in (usually younger) patients with pulmonary arterial hypertension than in older patients with COPD.(2,3)
 
CLINICAL MESSAGE
 
Although the 6MWT provides limited information regarding the underlying mechanisms of exercise intolerance, it can be clinically useful to assess (a) functional capacity; (b) the severity of walking-induced hypoxemia, including the need for exertional O2 supplementation; (c) the symptoms contributing to impaired exercise tolerance; and (d) potentially meaningful changes in walking capacity over time, either spontaneous changes or changes secondary to interventions. Akin to exercise-based evaluations that are more elaborate, all subjective and objective data should be interpreted in light of the clinical context and the limitations of the method (Chart 1).
 
REFERENCES
 
1.            ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test [published correction appears in Am J Respir Crit Care Med. 2016 May 15;193(10):1185]. Am J Respir Crit Care Med. 2002;166(1):111-117. https://doi.org/10.1164/ajrccm.166.1.at1102
2.            Holland AE, Spruit MA, Troosters T, Puhan MA, Pepin V, Saey D, et al. An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease. Eur Respir J. 2014;44(6):1428-1446. https://doi.org/10.1183/09031936.00150314
3.            Moutchia J, McClelland RL, Al-Naamani N, Appleby DH, Blank K, Grinnan D, et al. Minimal Clinically Important Difference in the Six-Minute Walk Distance for Patients with Pulmonary Arterial Hypertension [published online ahead of print, 2023 Jan 11]. Am J Respir Crit Care Med. 2023;10.1164/rccm.202208-1547OC. https://doi.org/10.1164/rccm.202208-1547OC
4.            Batista KS, Cézar ID, Benedetto IG, C da Silva RM, Wagner LE, Pereira da Silva D, et al. Continuous Monitoring of Pulse Oximetry During the 6-Minute Walk Test Improves Clinical Outcomes Prediction in COPD. Respir Care. 2023;68(1):92-100. https://doi.org/10.4187/respcare.10091
5.            Neder JA. Six-minute walk test in chronic respiratory disease: easy to perform, not always easy to interpret. J Bras Pneumol. 2011;37(1):1-3. https://doi.org/10.1590/S1806-37132011000100001