Serum surfactant protein D and exhaled nitric oxide as biomarkers of early lung damage in systemic sclerosis

BACKGROUND: Interstitial lung disease (ILD) complicates the course of systemic sclerosis (SSc), representing the main cause of death in these patients. The identification of parameters that can predict the early onset and progression of ILD in SSc represents an unmet need in clinical practice. The study was designed to explore whether the surfactant proteins (SP) A and D may be used as noninvasive tools for the early identification of ILD in SSc. Alveolar exhaled nitric oxide (NO) was investigated as a surrogate marker of distal inflammation. METHODS: Unselected consecutive subjects newly diagnosed with scleroderma and subjects free of respiratory and systemic diseases were recruited. All patients underwent clinical, lung functional, radiological and biological assessments. RESULTS: 15 individuals affected by SSc (M/F: 3/12), and 10 healthy subjects (M/F: 3/7) participated to the study. The serum SP-D values were 115.3 +/- 81.36 ng/mL in SSc subjects and 32 +/- 11.9 ng/mL, in healthy controls (P=0.004). The concentrations of scrum SP-A were not statistically different between groups. Scrum SP-D inversely correlated with FEV 1% predicted (r(s)=-0.29: P=0.004). FVC% predicted (r(s)=-0.20; P=0.02) and DLCO% predicted (r(s)=-0.36: P=0.001). Alveolar NO concentrations were significantly different between SSc and control subjects (6.5 +/- 12.9 ppb vs. 2.2 +/- 1.3 ppb, respectively; P=0.001), and positively associated with the levels of serum SP-D (r=0.60, P=0.03). CONCLUSIONS: These findings suggest that, in patients with scleroderma, SP-D and exhaled alveolar NO could represent novel non-invasive markers of early detection and activity of lung involvement.