© 2002 American Thoracic Society
How Acidopneic Is My Patient? A New Question in the Pulmonary LaboratoryDepartment of Pediatrics University of Virginia School of Medicine Charlottesville, Virginia In this issue of AJRCCM (pp. 1364–1370), Kostikas and coworkers (1) show that breath condensate pH is low in patients with moderate asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis, and that antiinflammatory treatment with inhaled corticosteroids is associated with increased breath pH. These findings are strikingly consistent with previously published data regarding patients with exacerbations of asthma and with COPD (2, 3). Their observations raise the possibility that a relatively simple breath pH test—analogous to measuring blood or urine pH—could be used in the pulmonary function laboratory to quantitate airways inflammation. We propose that this finding of acidic breath pH might be referred to as "acidopnea." The Kostikas group suggests that the low breath condensate pH in subjects with airways inflammation reflects, at least in part, the activity of myeloperoxidase and/or eosinophil peroxidase (1). These enzymes catalyze the formation of hypochlorous acid (HOCl; pKa, approximately 7.4) from H2O2 and Cl-. Indeed, they have shown elegantly that proton concentrations increase logarithmically with induced sputum neutrophil counts, as well as with breath H2O2 concentration, in both COPD and bronchiectasis. Furthermore, they showed that low pH in asthma is associated with high sputum eosinophil counts as well as with high levels of both H2O2 and the additional marker of oxidative stress, 8-isoprostane. On the other hand, HOCl formation is certainly not the only determinant of breath pH (2, 4–6). There is a fascinating gap between pH 7.4 and 7.5 in which there are no data points (1, 2), likely reflecting "silent buffers" slightly above and below this range. Indeed, acid loads delivered to the airways from a variety of endogenous and exogenous sources appear to be handled by both ion transport and a variety of base and buffer systems—ranging from airway peptides and proteins to ammonia-generating glutaminase—to protect the epithelium from injury (4, 7–10). Breath condensate pH, in turn, is even more complex, reflecting at least (1) the concentrations, pKas, volatility, and solubility of these compounds (2–6) and (2) determinants of relative amounts of vapor and droplets, including Reynold's number and surface tension at different airway levels (4, 6). Indeed, increased volumes of acidic airway-lining fluid might be aerosolized with increasing severity of obstructive disease, potentially reflected by the close association between breath pH and forced expiratory volume at one second (1). In this context, it is striking that, empirically, breath condensate pH measurement is highly reproducible and informative with regard to disease activity. The low breath condensate pH values in Kostikas and colleagues' article (1) are clearly not an artifact of vapor-phase CO2 depletion associated with hyperventilation. Indeed, these authors validate that deaeration—removing CO2 from the condensate sample—stabilizes the final pH value (1, 2). Furthermore, if subjects are asked voluntarily to hyperventilate or breathe 5% CO2, the deaerated breath condensate pH is not affected (10). In this regard, it is important to realize that (1) experimental model systems in which two or three buffers are studied in isolation—particularly if examined at nonphysiological concentrations—cannot predict the complex buffering system in the lung in vivo, and that (2) conclusions regarding breath pH should not be drawn from observations made on a small number of outliers using insensitive assays and condensates variably contaminated with saliva after long collection times (6). As Kostikas and coworkers point out (1), low pH could have several adverse effects in the airways, including epithelial dysfunction, impaired ciliary motility, bronchoconstriction, cough, altered mucous viscosity and augmented inflammation (1, 2). Therefore, acidopnea may be not only a marker for airway inflammation but may also be relevant to the pathophysiology of airways obstruction. On the other hand, airways acidification could be appreciated teleologically to have a role in innate host defense (2, 9). For breath condensate pH to be useful as a test for airways inflammation in clinical practice, additional issues need to be explored. For example, the complex determinants of acidopnea need to be clarified mathematically, ideally using modeling systems analogous to those for expired NO analysis (11, 12), and compared directly with bronchoscopic measurements. Furthermore, specimen collection, which often takes in excess of 15 minutes and is subject to oral contamination with gravity-based collection systems, needs to be more efficient. Indeed, it would be ideal to have a breath collection system that patients could use at home for longitudinal assessment. However, the elegant work of Kostikas and coworkers (1) has taken us a large step closer toward wanting to know the answer to this clinical question: "How acidopneic is my patient?" Acknowledgments This work was funded by the Henry B. Wallace Foundation, the National Institutes of Health (RO1 HL 69170 and RO1 HL 59337), and the National Institutes of Health Asthma Center. REFERENCES
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