Effects of Inhaled Prostaglandins E1, E2 and F2α on the Airway Resistance of Healthy and Asthmatic Man

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Abstract
1. Changes in specific airway conductance after the inhalation of aerosols of prostaglandins (PG) E1, E2 and F2α were investigated in healthy and asthmatic subjects. 2. Inhalation of 155 nmol (55 μg) of PGE1 or 156 nmol (55 μg) of PGE2 resulted in consistent minor bronchodilatation in healthy subjects, but in asthmatic patients airway conductance increased significantly, along with subjective improvement. Isoprenaline (988 nmol; 550 μg) 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 PGE2 were highly irritant to inhale. It was concluded that this made them unsuitable for therapeutic use. 3. Prostaglandin F2α inhalation resulted in a dose-related bronchoconstriction in healthy and asthmatic subjects. Asthmatics were approximately 150 times more sensitive to PGF2α than were the healthy subjects but there was very wide and significant variation 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 PGF2α 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, PGE2 and isoprenaline on PGF2α-induced bronchoconstriction were investigated in healthy subjects. Prostaglandin E2 reversed PGF2α-induced bronchoconstriction, as did isoprenaline, but prior treatment with the other drugs had no effect in preventing bronchoconstriction.

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