Background Respiratory failure is a life-threatening and unpredictable complication of systemic sclerosis (SSc). A study was undertaken to assess the value of alveolar nitric oxide (NO) in predicting the risk of lung function deterioration leading to respiratory failure or death in patients with SSc.

Methods 105 patients with SSc were enrolled in this prospective cohort and were followed longitudinally over a 3-year period during which the risk of occurrence of deleterious events was analysed according to alveolar concentration (C_Ano), conducting airway output (J′_awno) and fractional concentration (F_Eno_0.05) of exhaled NO measured at inclusion. Comparison was made between each NO parameter to predict the occurrence of deleterious events, defined as a 10% decrease in total lung capacity or forced vital capacity from baseline, or death.

Results The area under the receiver operating characteristic curve of C_Ano to predict the occurrence of the combined events was 0.84 (95% CI 0.76 to 0.92; p<0.001), which was significantly higher than those of J′_awno and F_Eno_0.05 (p<0.001). A cut-off of C_Ano of 5.3 ppb had a sensitivity of 88% and a specificity of 62% for the prediction of the occurrence of combined events during follow-up, and was validated in an independent cohort of patients with SSc. Combined events occurred more frequently in patients whose C_Ano was >5.3 ppb. The adjusted HR for patients with C_Ano >5.3 ppb was 6.06 (95% CI 2.36 to 15.53; p<0.001). C_Ano accurately predicted the occurrence of combined events irrespective of forced vital capacity values or the presence of interstitial lung disease at baseline.

Conclusions Increased C_Ano accurately identifies patients with SSc with a high risk of developing lung function deterioration and may help to initiate early appropriate treatment.