Standardization of the collection of exhaled breath condensate and exhaled breath aerosol using a feedback regulated sampling device

Brett R Winters,Michelle M Angrish,Joachim D Pleil,Terence H Risby,Matthew A Stiegel,Michael C Madden

doi:10.1088/1752-7163/aa8bbc

Abstract

Exhaled breath condensate (EBC) and associated exhaled breath aerosols (EBA) are valuable non-invasive biological media used for the quantification of biomarkers. EBC contains exhaled water vapor, soluble gas-phase (polar) organic compounds, ionic species, plus other species including semi- and non-volatile organic compounds, proteins, cell fragments, DNA, dissolved inorganic compounds, ions, and microbiota (bacteria and viruses) dissolved in the co-collected EBA. EBC is collected from subjects who breathe ‘normally’ through a chilled tube assembly for approximately 10 min and is then harvested into small vials for analysis. Aerosol filters without the chilled tube assembly are also used to separately collect EBA. Unlike typical gas-phase breath samples used for environmental and clinical applications, the constituents of EBC and EBA are not easily characterized by total volume or carbon dioxide (CO2) concentration, because the gas-phase is vented. Furthermore, EBC and associated EBA are greatly affected by breathing protocol, more specifically, depth of inhalation and expelled breath velocity. We have tested a new instrument developed by Loccioni Gruppa Humancare (Ancona, Italy) for implementation of EBC collection from human subjects to assess EBC collection parameters. The instrument is the first EBC collection device that provides instantaneous visual feedback to the subjects to control breathing patterns. In this report we describe the operation of the instrument, and present an overview of performance and analytical applications.

Highlights

There has been significant interest in the ability of breath analysis to identify target compounds and trends in the constituents of exhaled breath as a tool for diagnosing and monitoring medical conditions, and for discovering a growing number of biomarkers that might indicate recent environmental exposures or preclinical disease state [1,2,3]
exhaled breath condensate (EBC) volume Reducing variability in EBC sample volume and biomarker concentration is a key goal for the standardization of breath analysis
The variability of EBC volume using the Loccioni instrument was notably reduced in comparison to the spontaneous breathing EBC samples, regardless of collection time

Summary

Introduction

There has been significant interest in the ability of breath analysis to identify target compounds and trends in the constituents of exhaled breath as a tool for diagnosing and monitoring medical conditions, and for discovering a growing number of biomarkers that might indicate recent environmental exposures or preclinical disease state [1,2,3]. While there is significant interest in the collection and analysis of biomarkers in EBC for disease detection and monitoring, there are currently substantial issues with the collection and analysis of breath, in general, and in EBC with respect to inter-subject and intra-subject variability and a lack of standardization [15, 16] until very recent recommendations [28]. An instrument that assists in the control of a subject’s breathing rate and exhalation volume may be useful in reducing inter-subject and intra-subject variability within a specific study and for certain biomarkers

Methods

Results

Discussion

Conclusion