Inhaled PAF fails to induce airway hyperresponsiveness to methacholine in normal human subjects.
The effects of three increasing doses of platelet-activating factor (PAF) on airway caliber and methacholine bronchial responsiveness were studied. On separate occasions nine normal subjects inhaled a single cumulative provocation concentration of methacholine (control) causing a 40% fall (PC40 Vp30) in maximum expiratory flow rate at 70% of base-line vital capacity below total lung capacity during a partial forced expiratory maneuver or 100 or 200 micrograms PAF, and seven subjects inhaled a further dose of 400 micrograms PAF. Methacholine responsiveness was measured before, at 3 and 7 h, then on days 1, 2, 3, 4, 7, 10, and 14 after each challenge. The maximum falls in Vp30 appeared dose dependent, but a significant difference between the magnitude of the responses was only observed between the 400- and 100-micrograms PAF dose (P less than 0.05). During the control period repeated methacholine challenges resulted in a progressive increase in cumulative provocation concentration of an agonist causing a 20% fall in forced expiratory volume in 1 s from base line, reaching significance on days 1 and 2 (2.44- and 2.4-fold of base line, respectively, P less than 0.01) before returning to base line on day 7. No difference was seen in methacholine responsiveness after any of the three doses of PAF compared with that after the control. We conclude that PAF causes dose-dependent bronchoconstriction but does not change airways responsiveness to methacholine and that repeated high-dose methacholine challenge leads to loss of responsiveness to this agonist.
Lai
C K
CK
Immunopharmacology Group, Southampton General Hospital, United Kingdom.
Jenkins
J R
JR
Polosa
R
R
Holgate
S T
ST
D000280:Administration, Inhalation; D000328:Adult; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008448:Maximal Expiratory Flow Rate / Q000187:drug effects; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology*; D008875:Middle Aged; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D013610:Tachycardia / Q000139:chemically induced; D014797:Vital Capacity / Q000187:drug effects
D008688:Methacholine Compounds; D010972:Platelet Activating Factor; D016210:Methacholine Chloride