Effect of Inhaled Preservatives on Asthmatic Subjects: II. Benzalkonium Chloride

Abstract

Benzalkonium chloride has been used as a preservative in some antiasthma respirator solutions and is known to cause bronchoconstriction in asthmatic subjects. To increase understanding of how it causes bronchoconstriction, the characteristics of airway response in 28 asthmatic subjects were documented. Subjects inhaled histamine, in doses ranging from 0.03 to 7.8 mumol, or benzalkonium in doses ranging from 0.04 to 5.33 mumol on separate days. The dose of histamine or benzalkonium that caused a 20% fall in the 1-s forced expiratory volume (PD20FEV1) was measured. All subjects responded to histamine, with PD20FEV1 values in the range of 0.14 to 7.8 mumol and 17 responded to benzalkonium, with PD20FEV1 values in the range 0.35 to 5.55 mumol. Subjects who responded to benzalkonium were more sensitive to histamine (mean PD20FEV1 0.44 mumol) than subjects who did not respond (mean PD20FEV1 1.84 mumol) and, among the benzalkonium responders, there was a significant correlation between PD20FEV1 values for histamine and benzalkonium (r = 0.5, p less than 0.05). Inhalation of benzalkonium enhanced subsequent responses to histamine, causing a decrease in mean PD20FEV1 from 0.51 to 0.18 mumol histamine (p less than 0.001), but did not alter subsequent responses to benzalkonium. The response to benzalkonium reached a maximum 1 min after inhalation and was slow to recover, taking up to 60 min to return to baseline values. Response to benzalkonium was inhibited by 8 mg cromolyn sodium but not by 160 micrograms ipratropium bromide. The characteristics of the response to benzalkonium suggest a mechanism of action via release of mediators.