Scleroderma is a multisystem connective tissue disorder with a diverse range of presentations. Lung involvement is common and is the leading cause of morbidity and mortality.1 Pulmonary function impairment, quantified either by reduction in forced vital capacity or diffusing capacity for carbon monoxide, is an independent predictor of mortality.2–4 For every 10% decrease in the predicted diffusing capacity for carbon monoxide, the hazard of death increases by 20%.1 The presence of pulmonary arterial hypertension has also emerged as an important predictor of mortality in scleroderma.1,4,5
The six-minute walk test is frequently used to assess both prognosis and response to therapy in a wide range of pulmonary disorders.6,7 It is a commonly used outcome for clinical trials in idiopathic pulmonary fibrosis8,9 and is the accepted metric for assessing response to therapeutic interventions in pulmonary arterial hypertension.10 However, the role of the six-minute walk test in scleroderma remains unclear. Previous studies have found only weak-to-moderate associations between the six-minute walk distance (6MWD) and important clinical markers such as forced vital capacity, diffusing capacity for carbon monoxide and the extent of disease on high-resolution computed tomography.11–13 The lack of convincing data to support its validity has led to calls from some authors to abandon the 6MWD as an outcome measure for patients with pulmonary manifestations of scleroderma.14
Performance and interpretation of the six-minute walk test in scleroderma is challenging due to the other organs affected in this disease. Aside from pulmonary involvement, patients often have articular and soft tissue limitations that interfere with test performance. Lower extremity pain during walking may limit 6MWD and confound its interpretation.12 Other systemic manifestations such as left ventricular diastolic dysfunction15 and systemic inflammation13 have been associated with reduced 6MWD. The extent of deconditioning and peripheral muscle dysfunction have not been well documented in scleroderma; however, reduced physical activity levels and resultant loss of cardiovascular fitness are likely to contribute to exercise limitation in this group of patients with multisystem disease.16 It is possible that other variables measured during the six-minute walk test, such as the oxyhaemoglobin saturation, might be more sensitive to important clinical changes than the walking distance, as has been suggested in patients with idiopathic pulmonary fibrosis.17,18 However, the cutaneous manifestations of scleroderma, in particular the vasospastic predilection (Raynaud's phenomenon), may pose significant challenges in obtaining accurate non-invasive measurement of oxygenation during exercise.
In this issue of Respirology, Wilsher and colleagues present a study that advances our understanding of measurement procedures and interpretation for the six-minute walk test in people with scleroderma. Twenty-five individuals with scleroderma underwent two six-minute walk tests performed according to current standards6 with an interval of 1 week between testing. Outcomes measured were 6MWD, Borg score for dyspnoea and oxyhaemoglobin saturation measured by pulse oximetry (SpO2). The authors show that both 6MWD and Borg dyspnoea score are reproducible over a period of 1 week, albeit with quite wide limits of agreement for 6MWD. This confirms the reliability of the 6MWD in scleroderma using a more robust analysis than previous authors.11 However, it is in the measurements of oxyhaemoglobin saturation that the authors make a unique contribution to the literature. First, the authors demonstrate that earlobe oximetry is not feasible during the six-minute walk test in patients with scleroderma, with only seven participants showing reliable readings and an intraclass correlation coefficient for between-test reproducibility of 0.24. Reliability was better for forehead and finger oximetry (intraclass correlation coefficients 0.64 and 0.60) with Bland and Altman analysis showing a clear advantage to forehead oximetry. Most convincingly, oxyhaemoglobin desaturation during the six-minute walk test measured by forehead probe (but not finger probe) was correlated with forced vital capacity, diffusing capacity for carbon monoxide %predicted and radiological extent of disease on high-resolution computed tomography. These data suggest that in scleroderma, the SpO2 measured during the six-minute walk test might be a more important measure of clinical status than 6MWD and that this relationship may only become apparent when accurate and reliable measurement of SpO2 is performed.
The importance of desaturation during the six-minute walk test has previously been demonstrated in patients with idiopathic pulmonary fibrosis where a number of markers of desaturation have been associated with increased mortality.17,18 To date, the prognostic significance of desaturation during the six-minute walk test in patients with scleroderma has not been confirmed. In patients with interstitial lung disease associated with scleroderma, Swigris and colleagues19 showed that desaturation during a cardiopulmonary exercise test was a significant predictor of mortality even when controlling for forced vital capacity. Intriguingly, Swigris and colleagues obtained SpO2 measures using finger probes and were able to show good agreement with measures of oxyhaemoglobin saturation obtained simultaneously from an arterial line. The proportion of participants in this study with diffuse or limited scleroderma was not stated so it is difficult to compare the results with the current study of Wilsher and colleagues, in which almost 60% of patients had diffuse scleroderma. It is likely that differences in patient populations and equipment will influence the accuracy of SpO2 measurements during exercise testing, and this should be considered in the clinical setting.
The six-minute walk test is easy to perform in a clinical setting as it requires little equipment or monitoring. For patients with scleroderma who frequently experience musculoskeletal pain, a self-paced walking test may be more feasible and acceptable than other exercise tests that involve equipment such as a cycle ergometer or treadmill. The absence of an arterial line is a clear advantage for these patients with significant vascular pathology. However, ease of performance is no advantage if a test is not clinically important. The study of Wilsher and colleagues provides evidence that oxyhaemoglobin desaturation measured with a forehead probe may be the most important variable to record during the six-minute walk test in patients with scleroderma. These data confirm and extend previous observations about the relative importance of desaturation and 6MWD that were made in a less severely affected sample20 and provide new information regarding the type of monitoring that may be required to accurately assess SpO2 during exercise in scleroderma. The clinical picture is not yet complete—to fully understand the role of the six-minute walk test in the care of people with scleroderma, we must now move forward to determine whether desaturation during exercise has prognostic importance in people with scleroderma.