C. G. Lane

The effect of oral prostaglandin E1 on airway responsiveness in asthmatic subjects.

Prostaglandin E1 (PGE1) is a bronchodilator in humans, but the effect of this prostaglandin on airway responsiveness in asthmatic subjects is not known. The purpose of this study was to examine the effect of oral PGE1 treatment on airway responsiveness to inhaled histamine and methacholine in asthmatic subjects. The subjects had inhalation tests performed on separate study days over a period of 2 weeks. PGE1 (200 micrograms 4 times daily) or placebo was taken in a double-blind fashion for 4 consecutive days. Each week, after three days of treatment, a histamine or methacholine inhalation test was performed on one day, followed by an inhalation test with the alternative agonist the following day. Baseline forced expired volume in 1 s (FEV1) values were similar before each inhalation test on each study day (P = 0.81). However, both histamine and methacholine airway responsiveness decreased following PGE1 treatment. The mean provocative concentration of histamine causing a 20% fall in FEV1 (PC20 histamine) on the placebo day was 1.47 mg/ml (%SD 3.05) and was 2.35 mg/ml (%SD 2.72) (p less than 0.005) during PGE1 treatment period. Similarly the PC20 methacholine was 1.84 mg/ml (%SD 2.30) on the placebo day and was 2.53 mg/ml (%SD 2.06) during PGE1 treatment period (p = 0.025). This study demonstrates that oral PGE1, administered in doses which did not change airway caliber, can reduce airway responsiveness in mild asthmatics.

Effect of an inhaled thromboxane mimetic (U46619) on in vivo pulmonary resistance and airway hyperresponsiveness in dogs.

1. We investigated the role of thromboxane A2 in the airway hyperresponsiveness that follows the inhalation of ozone in dogs by examining the responses to an inhaled thromboxane analogue (U46619). 2. Measurements of pulmonary resistance were made in anaesthetized dogs; the concentration of inhaled agonist causing an increase of 5 cmH2O l‐1 s was calculated (provocative concentration). The effect of inhaled U46619 was studied on in vivo canine airway resistance, on airway responsiveness and on airways made hyperresponsive following the inhalation of ozone. 3. Inhaled thromboxane is a potent constrictor of the canine airway. The mean provocative concentration was 2.13 x 10(‐4) M, compared to acetylcholine which was 3.23 x 10(‐2) M. 4. Inhaled thromboxane did not result in the development of airway hyperresponsiveness to acetylcholine. Following U46619 inhalation the mean provocative concentration to acetylcholine was 3.92 x 10(‐2) M. 5. Canine airway was not hyperresponsive to inhaled thromboxane following the inhalation of ozone. This was not due to an inhibition of acetylcholinesterase as the dogs were hyperresponsive to carbachol (a muscarinic agonist not degraded by endplate cholinesterase). 6. These experiments do not support a role for thromboxane in the development of airway hyperresponsiveness following the inhalation of ozone in dogs.