The roles of pH and ionic species in sulfur dioxide- and sulfite-induced bronchoconstriction.
Sulfur dioxide (SO2) and sulfites are well-described causes of bronchoconstriction in persons with asthma that are chemically related and, therefore, may share a common mechanism of action. When either sulfur species dissolves in aqueous solutions, a pH-dependent equilibrium is established predominantly among bisulfite ion (HSO3-), sulfite ion (SO3=), and SO2. In addition, hydrogen ions may be released. To assess the relative bronchoconstricting potencies of these chemical forms and the role of acidity caused by the release of hydrogen ions in SO2- and sulfite-induced bronchoconstriction, we administered to 10 asthmatic subjects nebulized sodium sulfite (Na2SO3) solutions at pH 9 containing 95% sulfite, at pH 6.6 containing 80% bisulfite, and at pH 4 containing 99% bisulfite but greater than an order of magnitude more SO2 than the pH 6.6 solutions. Subjects inhaled increasing concentrations of aerosolized Na2SO3 at each pH during 1 min of tidal breathing. Subjects also breathed buffered acetic acid aerosols with the same acidity of the pH 4 Na2SO3 solutions to control for the airway effects of acid aerosols. To assess sensitivity to SO2 gas, subjects inhaled increasing concentrations of SO2 during eucapneic hyperpnea. Bronchoconstrictor response was assessed by measuring specific airway resistance (SRaw) before and after each challenge. Nine of the 10 subjects developed bronchoconstriction after inhaling the Na2SO3 aerosols at all 3 levels of pH and the SO2 gas. The mean concentration of Na2SO3 solution calculated to increase SRaw by 100% above baseline was significantly different (p less than 0.01) at the various levels of pH: pH 4 (0.17 mg/ml) less than pH 6.6 (0.49 mg/ml) less than pH 9 (2.10 mg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Fine
J M
JM
Cardiovascular Research Institute, San Francisco General Hospital, University of California 94110.
Gordon
T
T
Sheppard
D
D
D000280:Administration, Inhalation; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects*; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007477:Ions; D008297:Male; D013447:Sulfites / Q000494:pharmacology*; D013458:Sulfur Dioxide / Q000494:pharmacology*
D007477:Ions; D013447:Sulfites; D013458:Sulfur Dioxide