Endogenous airway acidification. Implications for asthma pathophysiology.
Airway concentrations of many reactive nitrogen and oxygen species are high in asthma. The stability and bioactivities of these species are pH-dependent; however, the pH of the airway during acute asthma has not previously been studied. As with gastric and urinary acidification, asthmatic airway acidification could be expected dramatically to alter the concentrations and bioactivities/cytotoxicities of endogenous nitrogen oxides. Here, we demonstrate that the pH of deaerated exhaled airway vapor condensate is over two log orders lower in patients with acute asthma (5.23 +/- 0.21, n = 22) than in control subjects (7.65 +/- 0.20, n = 19, p < 0. 001) and normalizes with corticosteroid therapy. Values are highly reproducible, unaffected by salivary or therapeutic artifact, and identical to samples taken directly from the lower airway. Further, at these low pH values, the endogenous airway compound, nitrite, is converted to nitric oxide (NO) in quantities sufficient largely to account for the concentrations of NO in asthmatic expired air, and eosinophils undergo accelerated necrosis. We speculate that airway pH may be an important determinant of expired NO concentration and airway inflammation, and suggest that regulation of airway pH has a previously unsuspected role in asthma pathophysiology.
Hunt
J F
JF
Divisions of Pediatric Respiratory Medicine, Pediatric Hematology/Oncology, and Allergy, Asthma and Immunology, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
Fang
K
K
Malik
R
R
Snyder
A
A
Malhotra
N
N
Platts-Mills
T A
TA
Gaston
B
B
D000136:Acid-Base Equilibrium / Q000502:physiology*; D000403:Airway Resistance / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology; D001249:Asthma / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D004804:Eosinophils / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009569:Nitric Oxide / Q000502:physiology*; D020545:Respiratory Mucosa / Q000503:physiopathology
D009569:Nitric Oxide