title: Buffering airway acid decreases exhaled nitric oxide in asthma.
abstract: 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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatric Respiratory Medicine, The University of Virginia School of Medicine, Charlottesville, VA 22908, USA. bmg3g@virginia.edu
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gaston
authors.forename: Robin
authors.initials: R
authors.lastname: Kelly
authors.forename: Peter
authors.initials: P
authors.lastname: Urban
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Edward M
authors.initials: EM
authors.lastname: Henderson
authors.forename: Allan
authors.initials: A
authors.lastname: Doctor
authors.forename: W Gerald
authors.initials: WG
authors.lastname: Teague
authors.forename: Anne
authors.initials: A
authors.lastname: Fitzpatrick
authors.forename: Serpil
authors.initials: S
authors.lastname: Erzurum
authors.forename: John F
authors.initials: JF
authors.lastname: Hunt
mesh_terms: D000143:Acids; D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001826:Body Fluids / Q000737:chemistry / Q000187:drug effects; D002021:Buffers; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects*; D008297:Male; D009330:Nebulizers and Vaporizers; D009569:Nitric Oxide / Q000378:metabolism*; D012129:Respiratory Function Tests; D020545:Respiratory Mucosa / Q000187:drug effects*; D012137:Respiratory System / Q000187:drug effects*; D012965:Sodium Chloride / Q000008:administration & dosage*
chemical_list: D000143:Acids; D002021:Buffers; D009569:Nitric Oxide; D012965:Sodium Chloride