Alveolar concentration of nitric oxide as a prognostic biomarker in idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis (IPF)is a chronic and progressive fibrotic lung disease leading to respiratory failure and death in 2–5 years from diagnosis. To date, clinical course of disease and prognosis cannot be predicted with an acceptable accuracy. Recently, alveolar concentration of nitric oxide (CaNO)has been proposed as a marker of severity of IPF, but its prognostic value in this setting is unknown. Aim of the study: To evaluate the reliability of CaNO as a prognostic biomarker in patients with IPF. Methods: In the Siena Referral Centre for Interstitial Lung Diseases, multiple-flows exhaled nitric oxide analysis was performed to measure CaNO in a cohort of 88 patients with IPF and in 60 healthy controls. In this population, we evaluate functional disease progression and survival according to the follow-up of our Centre. Clinical, functional and radiological data were collected at baseline to investigate correlations with CaNO levels. Results: IPF patients showed significantly higher levels of CaNO than healthy controls (p < 0.0001); CaNO was significantly correlated with many pulmonary functional parameters. Survival analysis showed that all patients with CaNO ≥6 ppb reported a significantly worse outcome. Disease progression, expressed as FVC time to decline to 10% (TTD10), occurred significantly earlier in patients with CaNO ≥ 9 ppb. Conclusion: We confirm that CaNO was significantly higher in IPF patients than in healthy controls and its correlation with functional parameters. Moreover, CaNO ≥6 and ≥9 ppb were significantly correlated with mortality and disease progression, respectively. These data suggest that CaNO, a non-invasive and reproducible biomarker, may predict disease progression and survival outcome in patients with IPF.