The Bronchoconstrictor Properties of Platelet-Activating Factor in Humans

Abstract

Platelet-activating factor (PAF) is an inflammatory mediator that causes bronchial smooth muscle contraction in vitro and in vivo in experimental animals. To characterize the effect of PAF on human airways, 6 normal subjects and 6 subjects with mild asthma inhaled PAF using a standard bronchoprovocation protocol and nebulizer concentrations ranging from 0.1 to 1000 ng/ml. Aerosolized PAF produced bronchoconstriction in 5 of 6 normal and 3 of 6 asthmatic subjects as defined by at least a 35% decrease in specific airway conductance (SGaw). However, in these same subjects, flow rates measured at 30% of vital capacity from a partial forced expiratory maneuver ( 30P) did not decrease at least 30% nor did the FEV₁ decrease by 20%. The 8 PAF responders were 5 to 836 times more sensitive to PAF than to methacholine when SGaw was used to assess the airway response. The relative airway sensitivity of the PAF nonresponders could not be assessed. Normal and asthmatic subjects could not be differentiated by their airway response to PAF, and there were no clinical features that differentiated PAF responders from nonresponders. The maximal airway response to PAF occurred within 2 to 3 min and lasted 15 to 45 min. There were no late reactions. Both normal (p < 0.01) and asthmatic (p < 0.05) subjects exhibited tachyphylaxis to PAF. Finally, PAF sensitized the airways of all normal subjects to methacholine, including the one PAF nonresponder (p < 0.02), but it did not sensitize the airways of the asthmatic subjects. These findings, especially the lack of hyperresponsiveness to PAF in asthmatic subjects and its ability to sensitize normal airways to another bronchoconstrictor, differentiate PAF from other putative mediators of asthma. Further studies are needed to define the role of PAF in asthma and its mechanism of action.