Background Lung involvement due to interstitial lung disease (ILD) and/or pulmonary arterial hypertension (PAH) is the most important cause of death in systemic sclerosis (SSc).
Objectives To assess the clinical usefulness of exhaled breath and exhaled breath condensate (EBC) biomarkers in the study of scleroderma pulmonary involvement (PI), and their correlation with disease progression.
Methods Fraction exhaled nitric oxide (FeNO) and exhaled carbon monoxide (eCO) measured in exhaled breath and pH, nitrite, nitrate and interleukin-6 in EBC were prospectively collected from 35 patients with SSc. Fourteen had established PI as presence of ILD or PAH, and 21 patients with no lung involvement. Pulmonary function tests (PFT) and clinical approaches were performed annually during 4 years of follow-up. A progression-free survival (PFS) analysis was performed defining end point as a decrease from baseline FVC of at least 10%, or a 15% diminution in DLCO, or death during follow-up.
Results There were no statistical differences in demographic data and the baseline characteristics between both groups. Median (interquartile range, IQR) age was 59.0 (42.0 to 68.0) years. Limited SSc was the most common cutaneous subset (28, 80%). The median of pulmonary duration disease was 1.7 years in PI group. Regarding lung function data at baseline, lower median FVC % and DLCO % values were identified in the PI group (76.5 vs. 94.2, p<0.01) and (45.6 vs. 71.7, p<0.001), respectively. Lower baseline pH levels were found in PI group (7.5 vs 8.0, p=0.04), with no other biomarker differences. Respecting the correlations between EBC biomarkers and PFTs during monitoring, lower pH levels were associated with lower DLCO % at 4 years of follow-up (r=0.45, p=0.01). Reduced FeNO levels were correlated with low FVC % at baseline (r=0.41, p=0.03), 4 years of follow-up (r=0.46, p=0.02) and with a decrease of FVC % (r=0.65, p<0.001) and DCLO % during monitoring (r=0.50, p=0.01). Among the PI patients, high eCO measurements were related to low baseline FVC % (r=0.69, p<0.01), and high IL-6 levels were correlated with low DLCO % at 4 years of follow-up (r= -0.64, p=0.03). The progression-free survival analysis identified that a pH equal or lower than 7.85 showed a decrease in lung function parameters or death during follow-up (log Rank p=0.03). FeNO levels equal or lower than 11.0 ppb were related to worse PFS (log Rank p<0.01) (figure).
Conclusions The pH and FeNO levels are implicated in the pathophysiology of the scleroderma lung. Exhaled breath and EBC may reflect the pulmonary inflammation with a non-invasive test, in which the biomarkers are correlated with a different outcome.
Disclosure of Interest None declared