Effects of inhaled platelet activating factor on pulmonary function and bronchial responsiveness in man

Lancet. 1986 Jul 26;2(8500):189-92. doi: 10.1016/s0140-6736(86)92489-x.

Abstract

Platelet activating factor (PAF), a phospholipid inflammatory mediator, was given as an aerosol to eight normal subjects. PAF caused a dose-dependent bronchoconstriction in all subjects. This did not correlate well with responsiveness to methacholine. Some subjects showed tachyphylaxis to PAF-induced bronchoconstriction. No subject had a late bronchoconstriction response. Transient facial flushing and an increase in heart rate (mean 7 beats/min) occurred but there was no consistent change in blood pressure. Lyso-PAF, the inactive precursor and major metabolite of PAF, had no effect on pulmonary or cardiovascular responses. Six of the subjects took part in a double-blind, randomised, placebo-controlled, crossover study in which bronchial responsiveness to methacholine was measured over the 3 days after administration of PAF or lyso-PAF. PAF had a greater effect in raising responsiveness (p less than 0.01). Its maximum effect occurred at 3 days and returned to baseline in 1 to 4 weeks. PAF may contribute to the pathogenesis of bronchial hyperresponsiveness, which is the most characteristic abnormality in asthma.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aerosols
  • Bronchi / drug effects*
  • Bronchi / physiology
  • Clinical Trials as Topic
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Synergism
  • Heart Rate / drug effects
  • Humans
  • Lung / drug effects*
  • Lung / physiology
  • Lung Volume Measurements
  • Male
  • Methacholine Compounds / administration & dosage
  • Methacholine Compounds / pharmacology
  • Platelet Activating Factor*
  • Random Allocation
  • Time Factors

Substances

  • Aerosols
  • Methacholine Compounds
  • Platelet Activating Factor