Reviews and Feature Articles: Rostrums
Exhaled breath condensate: An evolving tool for noninvasive evaluation of lung diseaseā˜†,ā˜†ā˜†

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Abstract

Exhaled breath condensate (EBC) contains aerosolized airway lining fluid and volatile compounds that provide noninvasive indications of ongoing biochemical and inflammatory activities in the lung. Rapid increase in interest in EBC has resulted from the recognition that in lung disease this easily sampled fluid has measurable characteristics that differ prominently from health. These assays have provided evidence of airway and lung redox deviation, acid-base status, and degree and type of inflammation in acute and chronic asthma, chronic obstructive pulmonary disease, adult respiratory distress syndrome, occupational diseases, and cystic fibrosis. Characterized by uncertain and variable degrees of dilution, EBC does not provide precise assessment of individual solute concentrations within native airway lining fluid. However, it can provide useful information when concentrations differ substantially between health and disease or are based on ratios of solutes found in the sample. Because they can be used to measure the targets of modern therapy, EBC assays are likely to become integral components of future clinical studies, and after further technical work is accomplished, they might be used to diagnose and monitor therapy in individual patients. (J Allergy Clin Immunol 2002;110:28-34.)

Section snippets

The physics and physiology of EBC: Aerosols and vapors

Two mechanisms have been proposed for aerosolization of airway lining fluid (ALF).*Turbulence, as evidenced by audible airflow, provides sufficient energy to the airway wall to aerosolize particles of ALF.15 If the energy provided to the airway wall increases-such as with increased ventilation during exercise-a greater yield and initial size of aerosol particles

Collection of EBC: General principles

EBC collection is a noninvasive process that is both simple and safe. As exhaled air cools below the dew point by transfer of heat to a chilled condenser surface, condensation occurs on available aerosolized ALF particles, and the thus-enlarged droplets of EBC impact and collect on the condenser wall. The systems reported in the literature generally collect 1 mL of EBC in 5 to 15 minutes. The volume collected depends on total expired air volume, condenser material and temperature, and

Collection devices

Most researchers have used custom devices, fashioned in individual laboratories, consisting of jacketed cooling pipes, tubes in buckets of ice, or glass chambers in ice with inhalation and exhalation ports. The least expensive and simplest technique involves exhaling through a tube that is suspended through a bucket of ice (Fig 1).

. Representation of a custom-built prototypical EBC collection device of the type used for many of the early studies. Air is exhaled through a tube, and droplets of

Variability in EBC assays

Although multiple reports suggest that assays for compounds of interest in EBC have sufficient intrasubject reproducibility, published reports of formal investigation into this issue are as yet scant. The one report to raise concerns about reproducibility unfortunately relied on homemade collection systems and difficult assays.5 The investigators' findings of marked variability in certain EBC substances raise questions about the collection and assay systems used in this particular study and

Absence of a gold standard

As of this writing, there have been only limited head-to-head comparisons of EBC assays with other methods of assessing airway biochemistry and inflammation, such as exhaled NO, bronchoalveolar lavage (BAL), induced sputum, and biopsy. In general, there does appear to be correlation among EBC assays and other assays of lung inflammation. It can be expected that like these other modalities, EBC will not precisely represent the ALF. Indeed, it is clear that ALF will be diluted in EBC, perhaps a

Current applications

As a research tool, EBC has several commendable features. Through use of appropriate equipment, samples have been collected at worksites, schools, hospitals, and clinics as well as in homes. After undergoing brief instruction, subjects can perform the sample collections multiple times in a day, completely unsupervised. Patients tend to find the experience interesting, and its negligible risk profile assures almost 100% successful recruitment into a study protocol. Frequent collections allow for

Future directions

Routine pulmonary function tests cannot contribute confidently to our assessment of the degree of inflammation and redox disturbance in the lung. To an increasing extent, however, our thinking and our therapies are directed to precisely those unmeasured disturbances. EBC assays expand on the promise of fractional exhaled NO concentration (FeNO) measurements to provide clinically useful methods by which to measure and monitor the biochemical and inflammatory processes underlying alterations in

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    ā˜†

    Supported by the American Academy of Allergy, Asthma and Immunology Education and Research Trust and GlaxoSmithKline. Dr Hunt is a Parker B. Francis Fellow in Pulmonary Research. He is a minority shareholder and director of Respiratory Research, Inc.

    ā˜†ā˜†

    Reprint requests: John Hunt, MD, Division of Pediatric Respiratory Medicine, Box 800386, University of Virginia, Charlottesville, VA 22908.

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