Most exhaled water is produced as gaseous water vapor, which can be collected in cooled condensers. The presence of nonvolatile solutes in these condensates suggests that droplets of respiratory fluid (RF) have also been collected. However, calculation of RF solute concentrations from condensates requires estimation of the dilution of RF droplets by water vapor. We used condensate electrolyte concentrations to calculate the dilution of RF droplets in condensates from 20 normal subjects. The total ionic concentration (conductivity) was 497 plus minus 68 (mean plus minus SEM) muM. Of this, 229 plus minus 43 muM was NH(4)(+), but little NH(4)(+) was collected from subjects with tracheostomies, indicating oral formation. The Na+ concentration in condensate ([Na+](cond)) averaged 242 plus minus 43 muM. Large variations in [Na(+)](cond) correlated well with variations of K+ in condensate ([K+](cond)) and Cl-) in condensate ([Cl-](cond)), and were attributed to differences in respiratory droplet dilution. Dividing condensate values of ([Na+] + [K+] ) by those of plasma indicated that RF represented between 0.01% and 2.00% of condensate volumes. Calculated values for Na+, K+, Cl-, lactate, and protein in RF were [Na+](RF) = 91 +/- 8 mM, [K+](RF) = 60 +/- 11 mM, [Cl-](RF) = 102 +/- 17 mM, [lactate](RF) = 44 +/- 17 mM, and [protein](RF) = 7.63 +/- 1.82 g/dl, respectively.
Exhaled breath condensates have been widely used to detect inflammatory mediators in the fluid that covers airway surfaces of patients with inflammatory lung disorders. This approach is much less invasive than bronchoalveolar lavage, but respiratory droplets are markedly diluted by large and variable amounts of water vapor. We estimated the dilution of respiratory droplets by comparing concentrations of nonvolatile, reference indicators (total nonvolatile cations, urea or conductivity) in 18 normal subjects with normal plasma concentrations by assuming similar concentrations in the respiratory fluid and plasma. The volatile cation, NH4+ (most of which is delivered as NH3 gas from the mouth), represented 93 +/- 3% (SEM) of the condensate cations. More than 99% of the NH4+ was removed by lyophilization, making it possible to use conductivity to estimate total nonvolatile ionic concentrations and facilitating analysis of urea. Conductivity was significantly correlated with electrolyte and urea concentrations. Estimates of dilution based on total cations, conductivity, and urea were not significantly different (cations: 20,472 +/- 2,516; conductivity: 21,019 +/- 2,427; and urea: 18,818 +/- 2,402). These observations suggest that the conductivity of lyophilized samples can be used as an inexpensive, simple, and reliable method for estimating dilution of nonvolatile, hydrophilic mediators in condensates.
The exhaled breath condensate (EBC) approach provides a convenient and noninvasive approach for sampling the pulmonary epithelial lining fluid (ELF). Increased EBC concentrations of more than a dozen inflammatory markers and hydrogen ions have been reported in lung diseases associated with inflammation. However, the usefulness of EBC is compromised by uncertainties concerning the sources of the EBC droplets and by the extreme and variable dilution of ELF droplets with condensed water vapor (ϳ20,000-fold). Reported increases in EBC concentrations may reflect proportionate increases in the total volume rather than the concentration of ELF droplets in the collected samples. Conclusions regarding ELF concentrations can only be made if this dilution is estimated with a dilutional indicator (e.g., conductivity of lyophilized EBC). In normal EBC samples, pH is effectively set by oral contamination with NH 3, and EBC pH cannot provide reliable information regarding ELF pH in normal subjects. Acidification of EBC observed in asthma and other conditions may reflect acidification of ELF, decreases in NH 3 added to the EBC, and/or the presence of gastric droplets in the EBC.
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