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Platelet activating factor does not cause a reproducible increase in bronchial responsiveness in normal man
D A Spencer1, S E Green, J M Evans
1Department of Thoracic Medicine, King's College School of Medicine and Dentistry, London, U.K.
Summary
Inhaled Platelet-Activating Factor (PAF) caused minor airway constriction and temporary neutrophil changes in most subjects. However, PAF did not significantly increase bronchial responsiveness, suggesting limited clinical relevance for asthma research.
Area of Science:
- Pulmonary Medicine
- Immunology
- Pharmacology
Background:
- Platelet-Activating Factor (PAF) is implicated in inflammatory airway diseases.
- Understanding PAF's acute effects on airway calibre and responsiveness is crucial.
Purpose of the Study:
- To assess the reproducibility of inhaled PAF's acute effects on airway calibre and neutrophil count.
- To investigate if inhaled PAF increases bronchial responsiveness in normal subjects.
- To compare PAF's effects with its precursor, lyso-PAF.
Main Methods:
- Six healthy subjects inhaled PAF and lyso-PAF on separate occasions.
- Airway calibre (sGaw, Vmax30) and neutrophil counts were measured.
- Bronchial responsiveness to methacholine was assessed over two weeks post-challenge.
Main Results:
- PAF induced bronchoconstriction and transient neutropenia in 5/6 subjects.
- Reproducibility of PAF's effects varied in one subject.
- No significant increase in bronchial responsiveness to methacholine was observed.
- Lyso-PAF inhalation caused no significant acute effects or changes in responsiveness.
Conclusions:
- Acute effects of inhaled PAF on bronchial responsiveness in humans are minimal and likely not clinically significant.
- This model is not suitable for studying bronchial hyperresponsiveness mechanisms or for preclinical assessment of anti-asthma drugs.