Ventilatory inefficiency limits 6-min walked distance in systemic sclerosis-associated interstitial lung disease

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) impacts cardiopulmonary systems and exercise capacity serves as a marker of disease severity. While the six-minute walking test (6MWT) is widely used to assess physical performance, its limitations to assess the cardiopulmonary function remain unresolved in SSc-ILD patients. This study aimed to investigate cardiorespiratory adaptations during the 6MWT, hypothesizing that ventilatory inefficiency is related to exercise capacity in SSc-ILD patients. We recruited 23 female SSc-ILD patients and 13 age- and sex-matched healthy controls (HC). Inclusion criteria included SSc diagnosis (limited or diffuse cutaneous subset) with mild-to-moderate associated ILD. Participants performed 6MWT with combined cardiopulmonary exercise testing (CPET) assessment using a wearable metabolic system to measure ventilatory and gas exchange parameters, including minute ventilation (VE), respiratory frequency (Rf), tidal volume (Vt), and ventilatory equivalent for CO₂ (VE/VCO₂). SSc-ILD patients exhibited increased Rf and VE during the initial minutes of exercise and during recovery compared to HC. Despite similar walking distances, SSc-ILD demonstrated higher VE/VCO₂ during the 6MWT. VE/VCO₂ was negatively correlated with 6MWT distance (6MWD) in SSc-ILD but not in HC. Patients walking more than 474 m (median) presented higher VE/VCO₂ than HC with same 6MWD. SSc-ILD patients showed a general impaired ventilatory efficiency during 6MWT. The main result suggests that exercise capacity is not only linked to global cardiovascular adaptation but also to ventilatory performance. These findings underscore the importance of incorporating CPET metrics to cardiorespiratory assessments to improve clinical understanding and assessment of SSc-ILD.