Background No established biomarkers are available to guide the treatment of chronic interstitial lung diseases (ILDs). Nitric oxide reflects the inflammation in the airway, and fractional exhaled nitric oxide (FeNO) is a non-invasive and reproducible biomarker in lung-disease diagnosis and treatment. Whether FeNO can help manage ILDs remains uncertain. This study aimed to determine the role of FeNO in ILDs and the association between FeNO and ILD subtype. Methods 53 patients with ILDs were retrospectively recruited. Patient characteristics, FeNO values, blood tests for inflammatory markers, and pulmonary function test data were obtained. ResultsThis group of patients with ILDs had decreased vital capacity(VC)and total lung capacity(TLC) of 71.75 ± 17.58% and 75.27 ± 14.07%, respectively. The diffusion capacity of the lung for carbon monoxide(DLCO) also declined, with an average level of 38.15 ± 11.10%. The average FeNO value was 20.34 ± 9.97 ppb. According to the characteristics of chest computed tomography, patients were divided into usual interstitial pneumonia (UIP)-ILD (n = 24) and non-UIP-ILD (n = 29). The FeNO value in the UIP-ILD group was 12.58 ± 3.63 ppb. This value was significantly lower than that of the non-UIP-ILD group (26.62 ± 8.61 ppb, P<0.0001).According to the etiology, all patients with ILDs were divided into connective tissue diseases associated with interstitial lung disease (CTD-ILD) (n = 30) and non-CTD-ILD (n = 23). There were more female patients in CTD-ILD group compared to non-CTD ILD group and patients in CTD-ILD group were younger. With regard to the FeNO, PFT values, and systemic inflammatory markers, no significant differences were observed between groups. In the overall ILD population, FeNO level correlated with blood eosinophil (r = 0.3066, P=0.0333), but no statistical significant correlations were observed between the FeNO and blood eosinophil percentage, IgE or systemic inflammatory markers. The FeNO cut-off value of 18.5 ppb showed a sensibility of 83.3% and a specificity of 95.8% in discriminating non-UIP-ILDs from UIP ILDs. Conclusions Our study suggested the importance of FeNO test in patients with ILDs. High FeNO levels may indicate the need of systemic treatment, and FeNO can be a helpful biomarker for ILD management.