Biomarkers in the exhaled breath condensate of healthy adults: Mapping the path towards reference values

The need for non-invasive assessment of airway inflammation is imperative, since inflammatory airway diseases, such as asthma and COPD, are characterized by variation in their clinical presentation throughout their course. Exhaled breath condensate (EBC) collection represents a rather appealing method that can be used to conveniently and noninvasively collect a wide range of volatile and non-volatile molecules from the respiratory tract, without affecting airway function or inflammation. Although promising, EBC is currently used only as a research tool, due to the lack of appropriate standardization and the absence of reference values. The large number of measurable biomarkers and the diversity of the used methodologies are some of the points that hamper its wide clinical application. This review focuses mainly on the presentation of normal values of the most widely studied EBC markers as reported by investigators that have used healthy subjects as controls or as a basic study population. These biomarkers include hydrogen peroxide, NO-related products, arachidonic acid metabolites and pH. From those biomarkers, the only one with established reference values in healthy subjects is EBC pH, whereas the majority of the rest need further refinement and standardization of the methodologies used. Different subpopulations and the effect of various factors on healthy subjects are also reported, in an effort to delineate future directions that may lead to the establishment of reference values.