Evaluation of oxidative stress biomarkers in idiopathic pulmonary fibrosis and therapeutic applications: a systematic review

Introduction: Idiopathic pulmonary fibrosis (IPF), a fatal lung disease of unknown origin, is characterized by chronic
and progressive fibrosing interstitial pneumonia which progressively impairs lung function. Oxidative stress is one of
the main pathogenic pathways in IPF. The aim of this systematic review was to describe the type of markers of
oxidative stress identified in different biological specimens and the effects of antioxidant therapies in patients with IPF.
Methods: We conducted a systematic search of publications listed in electronic databases (Pubmed, Web of Science,
Scopus and Google Scholar) from inception to October 2017. Two investigators independently reviewed all identified
articles to determine eligibility.
Results: After a substantial proportion of the initially identified articles (n = 554) was excluded because they were
duplicates, abstracts, irrelevant, or did not meet the selection criteria, we identified 30 studies. In each study, we
critically appraised the type, site (systemic vs. local, e.g. breath, sputum, expired breath condensate, epithelial lining
fluid, bronchoalveolar lavage, and lung tissue specimens), and method used for measuring the identified oxidative
stress biomarkers. Furthermore, the current knowledge on antioxidant therapies in IPF was summarized.
Conclusions: A number of markers of oxidative stress, with individual advantages and limitations, have been described
in patients with IPF. Nevertheless, trials of antioxidant treatments have been unable to demonstrate consistent benefits,
barring recent pharmacogenomics data suggesting different results in specific genotype subgroups of patients with IPF.