CAPÍTULO I Del Ejercicio
N. DE E A CONTINUACIÓN SE TRANSCRIBEN LOS ARTÍCULOS TRANSITORIOS DE LOS DECRETOS DE REFORMAS A LA PRESENTE LEY.
104 Chapter 8 M.C.Vonk1 Y.F. Heijdra2 J. Fransen1 P.N.R. Dekhuijzen2 P.L.C.M. van Riel1
F.H.J. van den Hoogen3
1 Departments of Rheumatology and 2 Pulmonary Diseases, Radboud University Nijmegen Medical
Centre, and 3 Sint Maartenskliniek Nijmegen, Nijmegen, The Netherlands
105 The six minute walk test in the assessment of systemic sclerosis
Abstract
Introduction: The six minute walk test (6MWT) is a reproducible sub maximal exercise test that has been found to be an independent predictor of mortality in pulmonary arterial hypertension (PAH). To date, the 6MWT has not been validated in systemic sclerosis (SSc). The objective of our study was to determine the 6MWT distance in SSc patients compared to expected values in healthy subjects and to determine differences in groups of SSc patients with and without pulmonary complications.
Methods: In 184 prospectively followed SSc patients a 6MWT, pulmonary function tests and echocardiography were performed.
Results: The median 6MWT distance was 429 m, which was significantly lower than the expected value of 557 m. After dividing the patients into 4 diagnosis groups, namely no pulmonary involvement, pulmonary fibrosis without pulmonary hypertension (PH), fibrosis and PH, and PAH, we found a decreased 6MWT distance in all groups. The lowest value of the 6MWT was present in patients with fibrosis and PH, followed by patients with PAH. Significant correlations of the 6MWT were found with various pulmonary function test results, but not with auto antibodies, disease duration or anaemia.
Conclusion: The 6MWT results are significantly lower in patients with SSc compared to healthy subjects. The impairment of the exercise capacity as measured by the 6MWT is most apparent in SSc-patients with pulmonary fibrosis and PH, but also present in scleroderma patients without pulmonary involvement.
Introduction
Systemic sclerosis (SSc, scleroderma) is an autoimmune connective tissue disease characterised by vascular lesions, induration and thickening of the skin, and fibrotic changes in internal organs 1;2. The mortality of SSc is high with a 5-year mortality rate of at least 30% 3. The leading
cause of disease-related mortality is pulmonary involvement consisting of pulmonary fibrosis with or without pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) 4;5.
Depending on the method of identification, pulmonary fibrosis is prevalent in up to 40% of the patients, whereas the prevalence of PAH is 12% 4;6. Recently, two studies have shown that
cyclophosphamide has a significant though clinically modest effect on pulmonary fibrosis in SSc patients 5;7. Furthermore, several treatments that successfully delay the progression of idiopathic
PAH such as epoprostanol, treprostinil, bosentan, sitaxentan, and sildenafil have become available 8-12, although their efficacy in SSc-associated PAH still needs to be defined. Evaluation
of the different treatment options usually consists, among others, of “time to clinical worsening” and six minute walk test (6MWT) distance. The 6MWT is a reproducible, safe and simple sub maximal exercise test that can be used to evaluate exercise limitation in patients with cardiac
106
Chapter 8
and pulmonary diseases 13. In patients with PAH, the 6MWT distance has been recognised as
a strong and independent predictor of mortality 14. To date, however, the 6MWT has not been
validated in SSc. Normal values derived from healthy American volunteers between 40 and 80 years of age, based on height, weight, age and gender, are used as gold standard to compare the measured values in patients 15. Recently, Buch and co-workers found that the 6MWT is
reproducible in patients with scleroderma related pulmonary fibrosis, but no information is available on scleroderma patients without pulmonary complications or patients with PAH 16.
Besides pulmonary complications, limitation of exercise capacity in SSc patients can be caused by cardiac involvement, deconditioning, fatigue and anaemia 17;18. Although these aspects have
not been studied intensively in SSc, it is likely that they also cause lower 6MWT results compared to normal subjects.
The main objective of our study was to determine the 6MWT distance in SSc patients compared to expected values from the healthy population and to determine differences in the 6MWT distance in groups of SSc patients with and without pulmonary complications. Also, we evaluated whether the 6MWT distance correlated with pulmonary function test results, SSc specific variables, age and organ complication associated parameters.
Patients and Methods
All adult patients with SSc, fulfilling either the preliminary American College of Rheumatology classification criteria 19 or the LeRoy criteria for early SSc 20 prospectively followed at the
Radboud University Nijmegen Medical Centre and St Maartenskliniek Nijmegen were asked to perform a 6MWT in the period between January 1st 2006 and January 1st 2007. Patients with
diffuse cutaneous SSc (DcSSc) and limited cutaneous SSc (LcSSc) were included. The 6MWT was performed according to the guidelines of the American Thoracic Society 13. Pulmonary function
tests were performed on the same day. The echocardiography with estimation of the systolic pulmonary arterial pressure (sPAP) and high-resolution computed tomography (HRCT-scan), to evaluate the presence of interstitial pulmonary involvement, were all performed within 2 months of the 6MWT. In those cases where the echocardiography revealed an estimated systolic pulmonary arterial pressure (PAP) ≥ 35 mmHg, or when other signs of pulmonary hypertension were found, a right heart catheterisation, the gold standard to diagnose PAH, was performed 21.
A diagnosis of PAH was established when at right heart catheterisation the mean PAP was > 25 mmHg at rest with a normal wedge pressure, ruling out left sided heart disease 22. To investigate
the origin of PH, a complete evaluation for those patients was performed, as described before
107 The six minute walk test in the assessment of systemic sclerosis
For the assessment of pulmonary interstitial disease, the HRCT-scan was scored at three levels: namely the midarch of the aorta, the main carina and 1 cm above the diaphragm. Both fibrosis and ground glass opacity (GGO) were graded between 0% to > 75% of the pulmonary surface, providing a score between 0 and 5, left and right lung scores were averaged, resulting in a total GGO and fibrosis score, both between 0 and 15 24;25.
Statistical analysis
For the calculation of the predicted 6MWT distance, the equation of Enright et al 15 was used. All
statistical analyses were performed using Statistical Package for Social Sciences (SPSS) version 14.0. Quantitative variables were summarised as median and full range. Groups were compared using the Mann-Witney U test or the Kruskal-Wallis test. Spearman’s correlation coefficient was applied to determine the correlation between 6MWT and pulmonary function test results. All statistical analyses were two-tailed and P values < 0.05 were considered to be significant.