Buffering airway acid decreases exhaled nitric oxide in asthma

Benjamin Gaston, Robin Kelly, Peter Urban, Lei Liu, Edward M. Henderson, Allan Doctor, W. Gerald Teague, Anne Fitzpatrick, Serpil Erzurum, John F. Hunt

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


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.

Original languageEnglish
Pages (from-to)817-822
Number of pages6
JournalJournal of Allergy and Clinical Immunology
Issue number4
StatePublished - Oct 2006


  • Buffer
  • airway acid
  • asthma
  • nitric oxide
  • nitrite


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