© 2003 American Thoracic Society
Breath Condensate AnalysisPerhaps Worth Studying, After AllPediatric Respiratory Medicine University of Virginia Health System Charlottesville, Virginia
My breath is corrupt, my days are extinct, the grave is ready for me. —Job 17:1 In this issue of AJRCCM (pp. 395–399), Corradi and coworkers (1) present evidence that breath condensate analysis identifies changes in the reduction/oxidation (redox) chemistry of water exhaled by children with acute asthma. Specifically, they show that levels of the oxidation byproduct, malondialdehyde, are substantially higher in breath condensate samples from children with acute asthma than they are in samples from control children. Furthermore, they show that levels of reduced glutathione (GSH) are low in the samples from children with acute asthma. Of note, they also show that malondialdehyde levels fall and GSH levels rise after 5 days of systemic corticosteroid treatment. These observations speak to recent controversies regarding the measurement of breath chemistry as an index of airways inflammation. The data of Corradi and coworkers (1) are consistent with those of several other groups, as recently reviewed (2). The data suggest that breath condensate analysis may be useful for identifying activity of airways disease and for monitoring the response to antiinflammatory therapy. There is growing interest in breath condensate analysis because it is simple, inexpensive, and noninvasive. Indeed, Corradi and coworkers confirm that breath condensate analysis is technically simple enough to be performed reproducibly by children (1). It must be emphasized, however, that the interpretation of breath condensate results is not straightforward. Several determinants of the concentration of a particular solute must be borne in mind, including its pKa, volatility, solubility, and concentration in aqueous and gas phases in the airways (2–4). In addition, the assays used for analysis need to be sensitive, reproducible, and able to be validated by complementary techniques (2). The work of Corradi and coworkers (1) demonstrates that condensate solute concentrations may be in the low nanomolar range, requiring highly sensitive assays for reproducible detection (1). These findings underscore the danger of drawing conclusions about the mathematical interpretation of breath condensate data based on theories generated from three or four data points/outliers, and/or based on a single, unsupported biochemical technique used to make measurements near the limit of detection (4). Conclusions may be formed (4) but later found to be incorrect (3, 5–7). The article by Corradi and coworkers (1) addresses, to some extent, a major concern about the interpretation of breath condensate analysis. Specifically, the data suggest that changes in the concentration of solutes in condensate samples obtained from subjects with obstructive lung disease are not simply a reflection of the degree of turbulent flow in the airways (1–4). Condensed vapor will invariably dilute aerosolized airway lining fluid droplets, and the more droplets in a sample, the more concentrated a given solute will appear. Corradi and coworkers (1), however, show that levels of GSH are lower than normal in condensate samples obtained during an acute asthma exacerbation (highly turbulent airflow), and increase after the subjects are treated with systemic corticosteroids (reducing airways obstruction and turbulent airflow). Further, they show that concentrations of breath condensate solutes are essentially independent of expiratory flow in the range 50 to 200 ml per second, whereas an increase in mean velocity should increase turbulent flow and particle aerosolization. These observations suggest that condensate concentration analysis is not simply a method for detecting the relative amount of airway lining fluid aerosolization. The observations of Corradi and coworkers (1) also add to a growing body of literature suggesting that oxidant stress may contribute to the pathophysiology of asthma. Oxidative injury occurs in the asthmatic lung as a result, at least in part, of recruitment and activation of eosinophils and neutrophils in the absence of appropriate antioxidant defenses (8–12). Thus, antioxidant therapy could be targeted to specific biochemical abnormalities, such as defective superoxide dismutation or excessive airways acidification (3, 6, 11), and tailored for delivery by aerosolization. In this regard, it is important to note that Corradi and coworkers (1) show that it is specifically malondialdehyde, but not other lipid aldehydes, that is present in high levels in the breath condensate of individuals with asthma. This may represent increased membrane breakdown and arachidonic acid formation—in the pathway to form leukotrienes and other inflammatory mediators—as opposed to nonspecific oxidative airways injury. The observation that GSH levels are low in condensates is consistent with evidence for increased oxidative stress, though it is surprising that the authors were unable to find oxidized glutathione. Dauletbaev and coworkers have shown that induced sputum GSH levels do not differ from normal in subjects with stable asthma (13), and the study by Corradi and coworkers (1) demonstrates that GSH levels increase with therapy. Taken together, these findings suggest that decreased levels of GSH in breath condensates, like acidopnea (3), may reflect an acute redox change associated only with an exacerbation of asthma. Indeed, there are conflicting results from studies of aerosolized GSH supplementation in asthma that may reflect, among other things, differences in subject acuity and/or disease severity (14, 15). In summary, the observations of Corradi and coworkers (1) show that breath condensate analysis (1) can noninvasively identify redox abnormalities in the breath of subjects with an acute exacerbation of asthma; (2) can demonstrate normalization of these redox abnormalities in the breath of subjects with asthma during corticosteroid treatment; (3) does not simply measure turbulent airflow and airways obstruction; and (4) can be easily performed by children. Taken together, this work suggests that breath condensate analysis may have a role in studying airway inflammation in asthma. REFERENCES
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