The Role of Titratable Acidity in Acid Aerosol-induced Bronchoconstriction1–3

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Abstract
We evaluated the importance of pH, titratable acidity, and specific chemical composition in acid aerosol-induced bronchoconstriction in 8 asthmatic subjects. We administered aerosols of HCl and H2SO4 at pH 2.0 in an unbuffered state and buffered with glycine. The buffered acids were given in order of increasing titratable acidity (defined as the number of ml of 1 N NaOH required to neutralize 100 ml of acid solution to pH 7.0). Each set of buffered or unbuffered acid aerosols was given on a separate day and each aerosol was inhaled through a mouthpiece during 3 min of tidal breathing. Bronchoconstriction was assessed by measurement of specific airway resistance (SRaw) before and after inhalation of each aerosol. SRaw increased by more than 50% above baseline in 1 of 8 subjects after inhalation of unbuffered HCl and in no subjects after inhalation of unbuffered H2SO4, even at pH 2.0. In contrast, SRaw increased by greater than 50% in all 8 subjects after inhalation of HCl and glycine at pH 2.0 and 7 of 8 subjects after inhalation of H2SO4 and glycine at pH 2.0. The mean titratable acidity required to increase SRaw by 50% above baseline was calculated for each challenge by linear interpolation; these values for H2SO4 and glycine (5.1 ml of 1 N NaOH) and HCl and glycine (2.2 ml of 1 N NaOH) were slightly, but significantly, different (p = 0.01) and were considerably higher than the titratable acidity of the unbuffered acids at pH 2 (1.0 ml of 1 N NaOH). These results demonstrate that titratable acidity and specific chemical composition as well as pH must be considered when evaluating the airway responses of asthmatics to acid aerosols.