Towards Reference Values for Malondialdehyde on Exhaled Breath Condensate: A Systematic Literature Review and Meta-Analysis

Many pathological conditions and certain airway exposures are associated with oxidative stress (OS). Malondialdehyde (MDA) is an end-product of the oxidation of lipids in our cells and is present in all biological matrices including exhaled breath condensate (EBC). To use MDA as a biomarker of OS in EBC, a reference interval should be defined. Thus, we sought to summarize reference values reported in healthy adult populations by performing a systematic review and meta-analysis using a standardized protocol registered in PROSPERO (CRD42020146623). Articles were retrieved from four major databases and 25 studies with 28 subgroups were included. Defining the distribution of MDA measured in reference populations with a detection combined with a separation technique still represents a challenge due to the low number of studies available, different analytical methods used, and questionable methodological qualities of many studies. The most salient methodological drawbacks have been in data collection and reporting of methods and study results by the researchers. The lack of compliance with the recommendations of the European Respiratory Society and American Thoracic Society was the major limitation in the current research involving EBC. Consequently, we were unable to establish a reference interval for MDA in EBC.