Does inhaled PAF cause airway hyperresponsiveness in humans?

Standardized challenge testing with pharmacological, physical and sensitizing stimuli in adults

“…The acute bronchoconstriction after P AF inhalation might be due to the secondary release of leukotrienes [212]. PAF has been shown to induce airway hyperresponsiveness in normal subjects [213], but this could not be confirmed by other investigators [214]. There is rapid tachyphylaxis to PAF inhalation.…”

An update on PAF

“…In contrast to these positive findings, several studies have now been published in which no increase in bronchial responsiveness has occurred following PAF inhalation in normal subjects [20][21][22][23]. Possible reasons for these divergent findings have been discussed previously in this journal [22,24] and include the dose of PAF, the method for assessing changes in bronchial responsiveness and the atopic status of the subjects. Perhaps the most obvious reason would be that higher doses of PAF might have been given in the positive studies, but this would not seem to be the case, as apparently higher doses were given in three of the negative studies [20,22,23], and in the remaining study similar doses to those described by Cuss [21].…”

“…Unfortunately, every centre has used a difl"erent experimental protocol involving various PAF formulations and preparation methods, nebulization and inhalation techniques so that such attempts at comparing PAF dose delivered to the airways are probably futile. The situation is further confused by diflerent studies describing the dose of PAF given as a single dose, the total cumulative dose, the dose range and the geometric mean dose [24]. Finally, ethical considerations imposed by wide intersubject variations in the acute response to this potentially injurious phospholipid have resulted in large diflerences in the doses of PAF administered between subjects within the same study, rendering meaningless any detailed comparison between studies.…”

Effect of Inhaled Platelet-Activating Factor on Bronchial Inflammation in Atopic Non-Asthmatic Subjects

“…Airway calibre was followed both as FEV, and as Vp30 as previ ously described [6]. Methacholine (Sigma, Poole, UK) was prepared in 0.9% sodium chloride (saline) to produce a range of doubling con centrations of 1-256 mg/ml.…”

“…However there is still controversy over whether this mediator can exert a similar effect on the human airways [6], Airway inflammation in asthma has been closely linked with bronchial hyperresponsiveness, in particular eosinophils are believed to play a pivotal role in this event. At low concentrations PAF is a potent chemoattractant for hu man eosinophils [7] and is able to prime granulocytes for mediator secretion [8], Thus if inhaled PAF induces air way hyperresponsiveness, one might expect to find evi dence of increased leucocyte recruitment associated with this response.…”