Exhaled Biomarkers in Idiopathic Pulmonary Fibrosis-A Six-Month Follow-Up Study in Patients Treated with Pirfenidone

J Clin Med. 2020 Aug 5;9(8):2523. doi: 10.3390/jcm9082523.

Abstract

The mechanism of action of pirfenidone in idiopathic pulmonary fibrosis (IPF) has not been fully elucidated. To offer additional insight, we evaluated the change in the cytokine profile in exhaled breath condensate (EBC) following a six-month treatment with pirfenidone in patients with IPF. EBC concentrations of interleukin (IL)-6, IL-8, IL-15, TNF-α and VEGF-A were assessed with ELISA and compared at baseline and after six months of pirfenidone treatment. Twenty-nine patients with IPF and 13 controls were evaluated at baseline. With the exception of IL-8 concentration, which was lower in patients with IPF when compared to controls (p = 0.005), the cytokine levels did not differ between the groups. Despite the use of a high sensitivity assay, IL-8 reached detectable values only in 24% of IPF patients. EBC analysis after six months of treatment with pirfenidone did not reveal any differences in the cytokine levels. The change in EBC vascular endothelial growth factor A (VEGF-A) correlated with the change in the 6 min walk distance (r = 0.54, p = 0.045). We conclude that a six-month treatment with pirfenidone did not significantly change the EBC cytokine profile. Our findings support the potential usefulness of VEGF-A as a marker in IPF. The low EBC IL-8 level in patients with IPF is a novel finding which needs confirmation in larger studies.

Keywords: antifibrotic treatment; exhaled breath condensate; interleukin; pulmonary fibrosis; vascular endothelial growth factor.