Exhaled NO predicts cyclophosphamide response in scleroderma-related lung disease

Cyclophosphamide (CYC) is not always effective in patients with scleroderma-related interstitial lung disease (SSc-ILD), hence the need for biomarkers able to predict beneficial responses to CYC therapy. We therefore assessed whether baseline alveolar concentration of nitric oxide (CANO) could predict the favourable response to CYC therapy in patients with SSc-ILD. Nineteen non-smoker patients with SSc-ILD, were enrolled and treated with 6 courses of CYC (0.75 g/m2/monthly) for lung function decline the year before inclusion, and followed-up for 2 years period. We assessed the proportion of favourable response to CYC, defined as improvement of forced vital capacity (FVC) or total pulmonary capacity (TLC) more than 10% between the inclusion and each following visit, according to the validated cut-off of CANO at 8.5 ppb identifying progressive SSc-ILD subset. At inclusion, 7 patients out of 19 had CANO >8.5 ppb. Clinical parameters were comparable between patients with high (>8.5 ppb) and low level of CANO (≤8.5 ppb). After CYC therapy, and during the follow-up, 9 out of 19 patients had favourable response to CYC therapy, 10 did not meet responder's criteria, from whom 4 patients died from respiratory failure. Six out of 7 patients with CANO >8.5 ppb at inclusion had favourable response to CYC therapy, while only 3 out of 12 patients with CANO ≤8.5 ppb responded favourably to CYC therapy (p=0.001). High level of CANO >8.5 ppb reflecting alveolar inflammation identify SSc patients with a greater chance to benefit from CYC treatment with a significant lung function improvement.