A review on airway biomarkers: exposure, effect and susceptibility

Abstract

Current research in pulmonology requires the use of biomarkers to investigate airway exposure and diseases, for both diagnostic and prognostic purposes. The traditional approach based on invasive approaches (lung lavages and biopsies) can now be replaced, at least in part, through the use of non invasively collected specimens (sputum and breath), in which biomarkers of exposure, effect and susceptibility can be searched. The discovery of specific lung-related proteins, which can spill over in blood or excreted in urine, further enhanced the spectrum of airway specific biomarkers to be studied. The recent introduction of high-performance ‘omic’ technologies – genomics, proteomics and metabolomics, and the rate at which biomarker candidates are being discovered, will permit the use of a combination of biomarkers for a more precise selection of patient with different outcomes and responses to therapies. The aim of this review is to critically evaluate the use of airway biomarkers in the context of research and clinical practice.

Keywords:

• airways
• biomarkers
• effect
• exposure
• susceptibility

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• Bronchoalveolar lavage is a valid method to determinate the internal dose following asbestos exposure.

• Induced sputum cell and mediator measurements are well validated, and normal ranges from large adult populations have been published.

• Induced sputum eosinophil count is now being widely carried out being a reliable method to assess airway inflammation, although it is performed in few centers.

• FeNO is the real noninvasive method to detect eosinophilic airway inflammation and to determine the likelihood of corticosteroid responsiveness, but tailoring of asthma treatment based on FeNO levels has not been shown to be effective in improving asthma outcomes.

• Methods used in collection and detection of EBC play significant roles in the accuracy and reliability of biomarker characterization; thus, it must be standardized in the view of collecting large number of samples.

• Clinical studies do not support EBC as a useful source of biomarkers, although novel methodologies may help to explore potential new ones.

• Hundreds of volatile organic compounds are released from human body fluids. Some of them are produced by endogenous metabolic processes in the body, and others are derived from the environment.

• Instruments for direct breath analysis based on mass spectrometry are bulky and relatively expensive.

• Developments of microsensor arrays may possibly result in cheaper direct reading options.

• Omic technology could be applied in the short future for understanding the normal human physiological processes and diseases.