The bronchoconstrictor properties of platelet-activating factor in humans.
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 micrograms/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 (V30P) 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 less than 0.01) and asthmatic (p less than 0.05) subjects exhibited tachyphylaxis to PAF. Finally, PAF sensitized the airways of all normal subjects to methacholine, including the one PAF nonresponder (p less than 0.02), but it did not sensitize the airways of the asthmatic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Rubin
A H
AH
Department of Medicine, Northwestern University Medical School, Chicago, Illinois.
Smith
L J
LJ
Patterson
R
R
D000293:Adolescent; D000328:Adult; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D005260:Female; D005540:Forced Expiratory Flow Rates; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology / Q000502:physiology*; D013618:Tachyphylaxis
D000336:Aerosols; D008688:Methacholine Compounds; D010972:Platelet Activating Factor; D016210:Methacholine Chloride