Introduction: Measuring airway pH is challenging and can be done directly or indirectly. Direct measurement requires bronchoscopy and is only reflective of the pH of the areas reachable by bronchoscopy. Indirect measurement can be done using exhaled breath condensate (EBC) pH or acute changes in exhaled nitric oxide (eNO). Both of these indirect methods are sensitive for detecting changes in airway pH but nonspecific with regards to the location within the airways they represent. Moreover, these indirect methods, while representative of airway pH, do not provide an exact measurement of airway pH. A non-invasive method for precisely measuring airway pH compartmentally would allow for detection of local airway pH imbalances and quantification of response to inhaled alkaline therapies. We hypothesized that inhalation of Optate, a safe aerosolized alkaline medication that increases airway pH, would result in compartmental changes in eNO representative of areas of deposition of inhaled Optate. We further hypothesized that we could use these compartmental changes in eNO in conjunction with a modified version of the Henderson-Hasselbalch equation to calculate the pH in each compartment. Methods: Compartmental eNO was measured in healthy human subjects and subjects with asthma before and immediately after inhalation of Optate. Compartmental eNO measurement consists of three exhalations at different flow rates: 30 mL/sec (representing tracheal eNO), 100 mL/sec (representing eNO from the middle airways), and 300 mL/sec (representing acinar eNO). % change was compared in each compartment of each subject after inhalation of Optate. Basline airway pH was directly measured during research bronchoscopy. These values were used in a modified Henderson-Hasselbalch equation to calculate compartmental airway pH. Results: eNO decreased significantly in all compartments (n = 10, p &lt; 0.001), but not equally. These values were succesfully entered into the modified Henderson-Hasselbalch equation to estimate regional airway pH. Conclusion: Compartmental eNO can be measured by collection of eNO at different expiratory flow rates, and changes differentially between compartments in which aerosol deposition differs. This may allow for the evaluation of compartmental airway pH changes in response to therapy, which can be calculated using a modified Henderson-Hasselbalch equation.

Using exhaled nitric oxide to evaluate and quantify regional airway response to inhaled medications

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