Buffering airway acid decreases exhaled nitric oxide in asthma

Background: The human airway is believed to be acidified in asthma. In an acidic environment nitrite is converted to nitric oxide (NO). Objective: We hypothesized that buffering airway lining fluid acid would decrease the fraction of exhaled NO (F _ENO). Methods: We treated 28 adult nonsmoking subjects (9 healthy control subjects, 11 subjects with mild intermittent asthma, and 8 subjects with persistent asthma) with 3 mL of 10 mmol/L phosphate buffered saline (PBS) through a nebulizer and then serially measured F _ENO levels. Six subjects also received PBS mouthwash alone. Results: F _ENO levels decreased after buffer inhalation. The maximal decrease occurred between 15 and 30 minutes after treatment; F _ENO levels returned to pretreatment levels by 60 minutes. The decrease was greatest in subjects with persistent asthma (-7.1 ± 1.0 ppb); this was more than in those with either mild asthma (-2.9 ± 0.3 ppb) or healthy control subjects (-1.7 ± 0.3 ppb, P < .001). Levels did not decrease in subjects who used PBS mouthwash. Conclusion: Neutralizing airway acid decreases F _ENO levels. The magnitude of this change is greatest in persistent asthma. These data suggest that airway pH is a determinant of F _ENO levels downstream from NO synthase activation. Clinical implications: Airway biochemistry modulates F _ENO levels. For example, nitrite is converted to NO in the airway, particularly the inflamed airway, by means of acid-based chemistry. Thus airway pH should be considered in interpreting clinical F _ENO values. In fact, PBS challenge testing integrates airway pH and F _ENO analysis, potentially improving the utility of F _ENO as a noninvasive test for the type and severity of asthmatic airway inflammation.