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

Abstract 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 (F E NO) is a marker of Th2 airway inflammation, but alveolar concentration of nitric oxide (C A NO) can be measured to assess Th2 inflammation in the periphery of the lung. The aim of this study is to assess whether C A NO 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. F E NO (28.5 ± 16 ppb vs 30.9 ± 17.2 ppb, p = 0.72) and C A NO (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. C A NO appeared reduced in patients with active sarcoidosis (2.1 ± 0.8 ppb vs 4.1 ± 3 ppb, p < 0.05). In conclusion, C A NO 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.