Characteristics of prostaglandin induced cough in man.

Abstract

Inhaled PGF2 alpha and PGE2 were evaluated for relative tussive activity to non-prostanoid tussive agents. In addition a comparison was sought between the present observations and those in the cat, the only laboratory animal which consistently coughs to prostanoids. Five healthy volunteers were repeatedly challenged at 90 min intervals with aerosols of PGE2 (100-500 micrograms ml-1) and tussive activity was monitored. In a second separate study again monitoring tussive activity 10 healthy volunteers inhaled aerosols of either PGF2 alpha (0.1-100 micrograms ml-1), PGE2 (0.1-100 micrograms ml-1), acetylcholine (0.1-50 mg ml-1) or citric acid (5-20% w/v) in a randomised procedure. Objective measurement of tussive activity was achieved using a throat microphone linked via a discriminator to a pen recorder. All four compounds produced two distinct phases of tussive activity, an early phase during challenge and a late phase 1-15 min post-challenge. Repeated challenges with PGE2, produced significant (P less than 0.01) tachyphylaxis to the late phase responses only. Both PGF2 alpha and PGE2 were approximately 1000 and 10,000 times more potent than acetylcholine and citric acid respectively for both phases of tussive activity. Tussive activity was accompanied with retrosternal soreness and tightness of the chest for PGE2, increased sputum for PGF2 alpha, and sore throats with citric acid. Although a correlation exists for man and cat with regards to the tussive potency and the early and late phases of PGF2 alpha activity no such correlation seems to exist for PGE2. The high tussive potency of the prostaglandins in man suggest that their local release in various respiratory pathophysiological conditions may be responsible for the accompanying coughs/irritancy.

Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators.

“…PGE 2 is also known to activate sensory endings in the lung. For example, inhalation of aerosolized PGE 2 elicits coughs and retrosternal soreness without significant change in baseline airway resistance (31,32) and augments the dyspneic sensation during exercise (31) in healthy human subjects. Inhalation of PGE 2 aerosol also induces reflex bronchoconstriction in asthmatic patients, despite its potent direct dilating effect on airway smooth muscles (27).…”

Physiology and treatment of cough.

“…37 The reason for the abnormal cough response in patients is uncertain. It is not merely a reflection of bronchial hyperreactivity as asthma in itself does not alter the cough reflex'0 and most of our patients with an increased cough reflex have a normal histamine response and no other symptoms of asthma.…”

Prostaglandin E2 Inhibits Eosinophil Trafficking through E-Prostanoid 2 Receptors

“…In the asthmatic lung, PGE 2 affects both airway smooth muscle and the inflammatory process; PGE 2 causes bronchial relaxation (14) and inhibits allergen induced bronchoconstriction (15), but it may also provoke bronchoconstrictor responses in some individuals (16) because of activation of C fibers and reflex cholinergic pathways (17). Moreover, PGE 2 can induce cough directly and sensitize the cough receptor (18). In humans and rats, PGE 2 reduces allergen-induced airway eosinophilia (19,20), abrogates eosinophil accumulation after passive cutaneous anaphylaxis in the guinea pig (21), and protects against bleomycininduced pulmonary fibrosis in mice (22).…”