Alveolar nitric oxide concentration as a potential biomarker of fibrosis and active disease in pulmonary sarcoidosis: a pilot study

Sarcoidosis is considered a T-helper (Th) 1 related disease, but a transition from Th1 to Th2 pathway activation has been postulated in sarcoidosis-associated pulmonary fibrosis (SAPF). Fraction of exhaled nitric oxide (FENO) is a marker of Th2 airway inflammation, but alveolar concentration of nitric oxide (CANO) can be measured to assess Th2 inflammation in the periphery of the lung. The aim of this study is to assess whether CANO can be considered a biomarker of SAPF or active pulmonary sarcoidosis. In this single-center retrospective study, we compared exhaled NO levels of patients with pulmonary sarcoidosis without fibrosis (N = 11) with those obtained from patients with SAPF (N = 15). Clinical data, as well as respiratory function tests, were also analyzed. FENO (28.5 ± 16 ppb vs 30.9 ± 17.2 ppb, p = 0.72) and CANO (4.4 ± 3.5 ppb vs 3.2 ± 1.7 ppb, p = 0.73) levels did not differ significantly between patients with or without SAPF, even when dividing them according to treatment or disease activity. CANO appeared reduced in patients with active sarcoidosis (2.1 ± 0.8 ppb vs 4.1 ± 3 ppb, p < 0.05). In conclusion, CANO cannot be considered a biomarker of SAPF. Its lower level in patients with active disease confirms the prevalence of Th1 inflammation in granuloma formation and suggests its potential role as a biomarker of active pulmonary sarcoidosis, but further studies with larger samples are needed to confirm this hypothesis.