© 2003 American Thoracic Society
Reporting Data on Exhaled Breath CondensateTo the Editor:We thank Dr. Risby for his most insightful editorial (1) on two articles on aldehydes in exhaled breath condensate from patients with chronic obstructive pulmonary disease and children with asthma (2, 3). However, we wish to point out that—contrary to what is stated in Dr. Risby's editorial—the units used in the two articles mentioned above are exactly the same, although abbreviated either as nM (nanomolar) or nmol/L (nanomoles per liter). Indeed, a solution described as 1.0 nM has a concentration of 1.0 nmol/L. Although these units are not approved by the General Conference of Weights and Measures, their use is substantial and is accepted worldwide—e.g., IUPAC, the American Institute of Physics (see http://www.aip.org/pubservs/style/4thed/toc.html at p. 39 of the manual), and the American Chemical Society (see Chem Res Toxicol 2002;15:9A). Regarding the need of a task force aimed at setting guidelines and basic requirements to collect exhaled breath condensate and express results, the American Thoracic Society has already established a joint task force with the European Respiratory Society, and a manuscript summarizing recommendations is being finalized (J.F. Hunt, personal communication). Other aspects related to collection and analysis of exhaled breath condensate remain unclear at this stage of research, including the following: (1) whether it should be considered a solution or a suspension, where particles and droplets do not form a unique phase with water; (2) whether the sampling device and procedure may affect its composition; and (3) whether measured concentrations need to be normalized for a still unidentified factor. The last issue is being debated and we are currently exploring a number of candidate variables to normalize data. Although a gold standard is not available yet, we do already know that the use of electrolytes proposed by Effros and colleagues (4) should be avoided. Indeed, we do not know the mechanism(s) underlying the formation of the vapor saturating the lower airways and affecting its composition, but we do know that ions are not extracted by the stream of evaporating water (distillation is a way to deionize water). This is why electrolytes cannot be proposed as a means to normalize the concentration of substances that, on the contrary, are found in exhaled breath condensate. Reasoning on patterns rather than on individual substances may provide a clue about underlying lung pathobiology and, within certain limits, might overcome the need for normalization.
a University Hospital of Parma Parma, Italy FOOTNOTES Conflict of Interest Statement: A.M. has no declared conflict of interest. M.C. has no declared conflict of interest. I.R. has no declared conflict of interest. Dr. Risby was given the opportunity to respond to this letter but declined to do so. REFERENCES
From the Authors: Dr. Mutti and colleagues have challenged our concept of measuring dilution of respiratory droplets in exhaled condensates (1). Our article emphasized a fundamental flaw in the condensate approach: investigators have failed to distinguish between changes in the number and volume of respiratory droplets entering the condensate and true changes in respiratory mediator concentrations. All molecules move into the exhaled air by either diffusion or convection. Volatile mediators (e.g., water vapor, ammonia, ozone, and perhaps other mediators) directly diffuse into the gaseous phase. As indicated in our article, nonvolatile indicators cannot be used to "standardize" volatile mediators. Furthermore, condensation represents an unreliable method of collecting volatile solutes, because the efficiency of their recovery and concentration in condensates will depend on multiple variables such as patterns of airflow, temperature, solubility, temperature, and pH. Nonvolatile molecules must be convectively introduced into the airstream as droplets. For hydrophilic mediators (e.g., peptides and proteins), dilution of total electrolytes or urea should provide reasonable estimates of the concentrations on respiratory surfaces and the efficiency of collection is relatively unimportant. For example, if the plasma urea concentration is 5 mmol/L and equals the respiratory fluid concentration, and condensate concentration is 0.5 µmol/L, the hydrophilic mediators must have been diluted by 10,000. It is conceivable that hydrophobic solutes will remain associated with lipid membranes in the exhaled air and condensates. Nevertheless, it would be important to know whether more aqueous respiratory droplets were collected from patients with inflammatory lung disease. Conclusions based on comparisons of inflammatory mediators with one another (rather than with noninflammatory solutes) are fraught with risk because an increase in the ratio between two mediators reflects either an increase in the numerator or a decrease in the denominator. Survival of the condensate approach will depend on sound chemical principles: water vapor is a gas and has no "composition," and evaporation does not form a "stream." It is the failure of ions to "evaporate" that makes them suitable indicators of droplet dilution. Unlike water vapor pressure, which remains relatively constant in exhaled air and keeps lung surfaces moist, respiratory droplet formation is a random and relatively infrequent event (there is usually less than 0.1 µl of respiratory fluid in each milliliter of condensate) and serves no known function other than spreading infections. Unless indicators of dilution are selected with well-defined criteria, the condensate approach inevitably will be abandoned because of persistent variability, inconsistency, and uncertain interpretation.
Medical College of Wisconsin Milwaukee, Wisconsin FOOTNOTES Conflict of Interest Statement: R.M.E. has no declared conflict of interest. REFERENCES
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