© 2003 American Thoracic Society
Dilution of respiratory solutes in exhaled condensatesTo the Editor:Effros and colleagues have drawn attention to the importance of dilution of breath condensates in a series of well-worked experiments (1). However, some of the reasoning from the data is flawed. The authors justify the calculation of dilution of the respiratory droplets found in condensate on the assumption that respiratory secretions have the same osmolarity as plasma. This is highly controversial, and there is no agreement between protagonists of the high salt (2) and isotonic hypotheses (3) as to the composition of epithelial lining fluid (ELF). Ion concentrations in another epithelial product, namely sweat, clearly varies considerably with disease, and there is no reason to believe that the same may not be true for ELF. Furthermore, there is at least some evidence that ELF ion composition may be affected by disease. Examples are bronchial infection and inflammation in cystic fibrosis as demonstrated in bronchoalveolar lavage (4) sputum (5), and exhaled breath condensate (6), and during exercise-induced asthma (7). Thus any assumption of a single set of ELF ion concentrations is likely to be flawed. Furthermore, to assume a concentration of sodium and potassium, and then attempt to back calculate to the real values from the assumed values is a circular argument, which makes no sense and cannot eliminate the problem caused by lack of knowledge of ELF ionic composition. What the authors have done is to highlight the orders of magnitude difference that may exist in dilution of condensates in the same individuals. This introduces much more significant errors than by making wrong assumptions within a relatively narrow physiological range of ion concentration. Would it not be more logical to try to control for the worst of the dilution errors by normalizing to an arbitrary sodium concentration of (say) 100 mmol, rather than plunge into attempts at further refinements based on assumptions that are likely to be spurious? Alternatively, dilution should be assessed from an ELF component whose concentration is known, and does not vary with disease.
Royal Brompton Hospital London, United Kingdom REFERENCES
From the Authors:We would agree with many of the comments of Zacharasiewicz and coworkers. In our recent paper (1), we specifically emphasized that our approach for calculating the dilution of respiratory droplets by water vapor in the condensate was based upon the common assumption that the respiratory fluid is isotonic. This assumption remains somewhat controversial, and alternative reference indicators will be needed to determine whether the condensate is indeed isotonic. We have investigated urea for this purpose because it rapidly equilibrates with fluid in the airspaces and is not appreciably produced, transported, or metabolized in the lungs (2). Unfortunately, most methods of detecting urea are based upon degradation of urea to NH3 by urease. Largely because of oral production, concentrations of NH4+ in the condensate are normally more than 20 times greater those of any other ions, making it difficult to detect NH4+ release from urea. These high NH4+ concentrations also make interpretation of condensate pH values problematic, because they may be influenced by events in the mouth.Our observation that condensate concentrations of Na+, K+ and Cl- are correlated over a larger range of concentrations (1) has proven to also be true over a more limited concentration range (less than 30 mmol/liter). The major objective of our publication was to indicate the importance of dilution in all studies of respiratory condensates. Unless or until better indicators of dilution can be developed, it would seem prudent to indicate concomitant Na+, Na+ + K+, and/or Cl- concentrations in the condensate in all studies of condensate mediator concentrations, so that artifacts associated with differences in dilution can be detected and minimized. Ideally, plasma concentrations should also be determined, but these tend to vary in a less than 10% range and have a relatively minor effect on the data.
Medical College of Wisconsin Milwaukee, Wisconsin REFERENCES
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