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.