1. Changes in specific airway conductance after the inhalation of aerosols of prostaglandins (PG) E1, E2, and F2alpha were investigated in healthy and asthmatic subjects. 2. Inhalation of 155 nmol (55 mug) of PGE1 or 156 nmol (55 mug) of PGF2 resulted in consistent minor bronchodilatation in healthy subjects, but in asthmatic patients airway conductance increased significantly, along with subjective improvement. Isoprenaline (988 nmol; 550 mug) inhalation resulted in a similar increase in conductance to that obtained after these two prostaglandins, whereas a control aerosol had no effect. In contrast to the isoprenaline aerosol, both PGE1 and PGF2 were highly irritant to inhale. It was concluded that this made them unsuitable for therapeutic use. 3. Prostaglandin F2alpha inhalation resulted in a dose-related bronchoconstriction in healthy and asthmatic subjects. Asthmatics were approximately 150 than were the healthy subjects but there was very wide and significant variantion in the sensitivity of the asthmatic subjects. In contrast the asthmatic subjects were only 8-5 times more sensitive to histamine than the healthy subjects with less variation in response of individual subjects. The reasons for the hyper-reactivity of asthmatic subjects to PGF2alpha is unknown and no correlation could be drawn between increased sensitivity and age, type of asthma, or treatment. 4. The effects of disodium cromoglycate, flufenamic acid, atropine methonitrate, PGF2 and isoprenaline on PGF2alpha-induced bronchoconstriction were investigated in healthy subjects. Prostaglandin E2 reversed PGF2alpha-induced bronchoconstriction, as did isoprenaline, but prior treatment with the other drugs had no effect in preventing bronchoconstriction.

The forced expiratory volume in one second (F.E.V.(1)) was measured in healthy and asthmatic volunteers and the inhalation of prostaglandin E(1) (PGE(1)) was compared with that of isoprenaline, using metered aerosols.In healthy volunteers PGE(1), either as the free acid or the neutral triethanolamine salt, did not affect the F.E.V.(1); the free acid was irritant to the upper respiratory tract. In five out of six asthmatic volunteers with reversible airways obstruction, inhalation of 55 mug of PGE(1) (triethanolamine salt) produced an increase in F.E.V.(1) comparable in both degree and duration to that produced by an inhalation of 550 mug. of isoprenaline sulphate.Though the triethanolamine salt was well tolerated in most of the asthmatic subjects studied, in one asthmatic subject this preparation caused coughing and there was a progressive reduction in the F.E.V.(1) associated with bronchospasm.

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SummaryExperiments were carried out in healthy male volunteers to investigate the effect of the inhalation of prostaglandin F2a (PGF2a) on airways resistance and the influence of the subsequent inhalation of prostagdin E2 (PGE2). Airways resistance, which reflects the tone of smooth muscle in the larger airways in man, was measured by total body plethysmography.The inhalation of PGF2a (40-60 ug) caused an increase in airways resistance in all subjects. Both PGE2 (55 ug) and isoprenaline (550 ,g) given by metered aerosol promptly reversed the bronchoconstriction induced by PGF2a, but isoprenaline was more effective in this respect.A role for these prostaglandins in the control of bronchial muscle tone is discussed. IntroductionProstaglandins affect human bronchial muscle in different ways depending on their structure and route of administration. Those of the E series relax bronchial muscle, and both prostaglandins E1 and E2 (PGE1 and PGE2) cause bronchodilatation in asthmatic subjects when given by metered aerosol (Cuthbert, 1969(Cuthbert, , 1971. On the other hand, those of the F series, and particularly prostaglandin F2a (PGF2a), are