Exhaled Breath Condensate: An Overview

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Exhaled breath condensate (EBC) is a promising source of biomarkers of lung disease. EBC is not a biomarker, but rather a matrix in which biomarkers may be identified, in that way equivalent to blood, sweat, tears, urine, and saliva. EBC may be thought of either as a body fluid or as a condensate of exhaled gas. The field of EBC research has advanced gradually, with the debates surrounding an emerging field helping to pose questions and gradually leading to answers. Conscientous assay technique will likely find in EBC any substance of substantially high enough concentration in the airway lining fluid.

Section snippets

Source of exhaled breath condensate biomarkers

Very little work has yet been done to help understand the nature and source of the exhaled particles and droplets that are part of the EBC matrix. That micron- and submicron-sized droplets emanate from the mouth or endotracheal tube in exhaled breath has been confirmed by laser particle counters [2], [3], and indeed such particles serve as the only explanation for the presence of clearly nonvolatile constituents in EBC, such as cytokines [4] and sodium ion [5]. How these particles form and

Particle size

One 10-μm particle entering a sample of EBC can supply 1,000,000 times the quantity of nonvolatiles to a sample of EBC as one 0.1-μm particle. There is skewing, however, of the particle sizes exhaled toward the smaller particles [3]. Overall, the relative contribution to EBC nonvolatile constituent of the different sized particles remains unknown.

Oropharyngeal contribution to exhaled breath condensate

In oral EBC collections, there is no reason to suspect that particles cannot be released from the oral and retropharyngeal mucosa into the airstream, with potential variably to contaminate what might otherwise be a pure lower airway sample. Furthermore, depending in part on the EBC collection equipment, gross or microscopic salivary contamination of EBC can and does occur [7]. Some subjects simply drool during collection, affirming the need for salivary trapping systems to be in place. Measures

Dilution

The airway lining fluid component of EBC is highly diluted by condensing vapor phase water. Estimates of the dilution of airway lining fluid particles in EBC range from 20- to 30,000-fold [10]; 2000- to 10,000-fold seems to be a generally accepted number [11]. There may be relevant day-to-day and sample-to-sample intrasubject variability in dilution, although debate occurs because the assays used for assessment of dilution are themselves a source of variability. As is common in much of medicine

Lack of gold standards of lung disease assessment or diagnosis with which to compare exhaled breath condensate measurements

There is currently no gold standard invasive or noninvasive method of determining absolute concentrations of airway lining fluid nonvolatile constituents with which EBC can be readily compared. For example, bronchoalveolar lavage is subject to its own dilution concerns. Microsampling techniques that draw fluid from the airway wall by capillary action or suction alter the fluid itself, creating a lung biomarker equivalent to the Heisenberg Uncertainty Principle. Induced sputum suffers similarly

Validation

EBC is often lumped together with exhaled nitric oxide in review articles and insurance company briefings, but from a validation standpoint technically is far behind exhaled nitric oxide [1]. This is not because exhaled nitric oxide is a better biomarker than EBC. One must remember that EBC is not a biomarker at all. Exhaled nitric oxide is one biomarker, whereas EBC is a matrix in which so many biomarkers have been identified that there is simply not the concentration of investigators studying

Collection of exhaled breath condensate

Interest in EBC lies first and foremost with its ease of collection in nearly any setting. Entirely noninvasive, it takes as little as five breaths to collect sufficient sample for assay, although in research practice, substantially longer collection times are often used to ensure sufficient sample is available for repeated analysis of multiple biomarkers. Ten minutes of tidal breathing yields 1 to 2 mm of sample, and is well tolerated. Some centers, including the author's, focus on one or two

Range of exhaled breath condensate biomarkers

Categorization of EBC biomarkers has been done in the past (Horvath Task Force [11]), although this is open to change. There are several potential categorizations, and biomarkers may fall into one or more of the following groups:

  • Categorization group 1

    • 1.

      Volatile compounds

    • 2.

      Nonvolatile compounds

    • 3.

      Nonvolatile compounds derived from volatile compounds

  • Categorization group 2

    • 4.

      Very-low-molecular-weight compounds

    • 5.

      Low-molecular-weight compounds

    • 6.

      Polypeptides

    • 7.

      Proteins

    • 8.

      Nucleic acids

  • Miscellaneous differentiation

    • 9.

      Lipid

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JH is a cofounder of Respiratory Research, which manufactures exhaled breath condensate collection equipment.

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