Systemic sclerosis (SSc) is a connective tissue disease characterized by autoimmunity, small vessel vasculopathy and excessive collagen deposition in the skin and internal organs. Pulmonary involvement is responsible for reducing the functional capacity to exercise and represents the main cause of death. The six-minute walk test (6MWT) is a simple, non-invasive, easy-to-perform, and reliable submaximal aerobic exercise test that can used in patients with advanced lung disease. Patients with SSc often have not only lung disease, but combinations of cardiopulmonary involvement, skin fibrosis, musculoskeletal damage, and joint disease, which can confound the 6MWT interpretation. As it is an independent predictor of SSc-related mortality, the 6MWT is a potentially useful tool in the assessment of outcomes along with pulmonary function tests (PFTs) and computed tomography. Currently, there is a huge concern about the need for early screening, search for new treatments and closer monitoring of patients with diffuse cutaneous systemic sclerosis-associated interstitial lung disease (dcSSs-ILD) before irreversible deterioration of lung function occurs.

To build a predictive model for the six-minute walk distance (6MWD) in women with dcSSs-ILD without pulmonary arterial hypertension.

This is a cross-sectional study in which 69 women with dcSSs-ILD underwent the 6MWT, Health Assessment Questionnaire-Disability Index (HAQ-DI), PFTs (including spirometry, measurement of pulmonary diffusion capacity for carbon monoxide-DLCO and measurement of respiratory muscle strength), handgrip strength (HGS) and quadriceps strength (QS).

The mean 6MWD was 447 ± 78 m, with 43.5% of the participants not reaching 80% of the predicted value. The 6MWT was positively correlated with HR (r = 0.418, P = 0.0004), forced vital capacity (r = 0.306, P = 0.011), DLCO (r = 0.360, P = 0.002), maximal inspiratory pressure (r = 0.268 , P = 0.029), and maximal expiratory pressure (MEP, r = 0.288, P = 0.019) and negatively with age (r = -0.378, P = 0.001), body mass index (BMI) r = -0.248, P = 0.039) and HAQ-DI (r = -0.438, P = 0.0001). In the multiple linear regression analysis, QS, BMI, DLCO, age and MEP explained 72% of the 6MWD variability.

In patients with dcSSs-ILD, alongside reduced pulmonary diffusion, deterioration in respiratory and peripheral muscle strength negatively impact performance during the 6MWT. Furthermore, the greater the age and BMI, the lower the 6MWD. Our results are promising and may become a contribution to future investigations aimed at new pharmacological therapies for dcSSs-ILD.

These findings may help the growing number of randomized controlled trials that have emerged in search of disease-modifying therapies for dcSSs-ILD, with the aim of incorporating the 6MWD as a clinical outcome measure.