Endogenous Airway Acidification . Implications for Asthma Pathophysiology

• Published in: American journal of respiratory and critical care medicine Vol. 161; no. 3; pp. 694 - 699
• Main Authors: HUNT, JOHN F, FANG, KEZHONG, MALIK, RAJESH, SNYDER, ASHLEY, MALHOTRA, NEIL, PLATTS-MILLS, THOMAS A. E, GASTON, BENJAMIN
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 01.03.2000; American Lung Association
• Subjects: Acid-Base Equilibrium - physiology; Airway Resistance - physiology; Apoptosis - physiology; Asthma - physiopathology; Biological and medical sciences; Bronchial Hyperreactivity - physiopathology; Chronic obstructive pulmonary disease, asthma; Eosinophils - physiology; Humans; Hydrogen-Ion Concentration; Medical sciences; Nitric Oxide - physiology; Pneumology; Respiratory Mucosa - physiopathology; Nitrogen oxide; Human; Corticosteroid; Respiratory disease; Pathogenesis; Antiinflammatory agent; Exploration; Asthma; Respiratory tract; Chemotherapy; Treatment; Nitric oxide; pH; Obstructive pulmonary disease
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/ajrccm.161.3.9911005

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.