No abstract

The effect of inhaled capsaicin, the irritant extract of pepper, on airway tone has been studied in humans. Inhaled capsaicin (2.4 X 10(-10) and 2.4 X 10(-9) mol) caused a dose-dependent fall in specific airways conductance (maximum fall 28 +/- 19 and 38 +/- 19%, respectively; means +/- SD, n = 17). This was maximal within 20 s of exposure and lasted for less than 60 s. There was no difference in the magnitude or duration of bronchoconstriction between normal, smoking, or asthmatic subjects. Capsaicin also caused coughing and retrosternal discomfort. On repeated exposure to capsaicin, there was no evidence for a reduced response (tachyphylaxis). Ipratropium bromide (0.25 mg by inhalation) significantly (P less than 0.05) reduced the bronchoconstriction (maximum falls 34 +/- 14 and 15 +/- 9% after saline and ipratropium bromide, respectively; means +/- SD n = 6), indicating that it was dependent on a cholinergic vagal reflex rather than on local release of substance P from nerves in the airway. Inhaled sodium cromoglycate (10 mg by nebulizer or 40 mg as a dry powder), however, had no significant effect on the bronchoconstrictor response. Capsaicin may be a useful tool for investigating nonmyelinated nerve reflexes in human airways.

Muscarinic receptors of the M2 subtype, which inhibit acetylcholine release from cholinergic nerves (autoreceptors), have been described in animal and human bronchi in vitro. We investigated whether these receptors may be involved in feedback inhibition of cholinergic reflex bronchoconstriction induced by sulfur dioxide (SO2) in seven nonasthmatic atopic subjects and in six mild asthmatic subjects. In a control experiment, total respiratory resistance (Rrs) was increased by 30 +/- 5% in nonasthmatic and by 60 +/- 18% in asthmatic subjects. In nonasthmatic subjects, pilocarpine, an agonist of muscarinic M2-autoreceptors, increased Rrs by 15 +/- 5% and addition of SO2 increased Rrs to 21 +/- 5% above base line, which was not significantly greater than after pilocarpine alone. Histamine gave a comparable bronchoconstriction (25 +/- 3% increase in Rrs) and SO2 further increased Rrs to 39 +/- 6% above base line (P less than 0.05). Thus pilocarpine appears to inhibit SO2-induced bronchoconstriction in nonasthmatic subjects, and this effect is not explained by an increase in airway tone. In asthmatic subjects, pretreatment with pilocarpine increased Rrs by 31 +/- 8% and SO2 further increased Rrs to 88 +/- 17% above base line. SO2 alone gave a 60 +/- 18% increase in Rrs. Our results suggest that feedback inhibitory muscarinic receptors may be present on cholinergic nerves in normal airways and that there may be a dysfunction of this feedback mechanism in asthmatic airways. This might be contributory to exaggerated cholinergic reflex bronchoconstriction in asthma.

1 The effects of inhaled nedocromil sodium and sodium cromoglycate on bradykinininduced bronchoconstriction have been studied in a double-blind, placebo controlled study, in eight mild asthmatic subjects. 2 The subjects attended on four occasions. Fifteen minutes after drug pre-treatment a bradykinin challenge was performed. Increasing concentrations were inhaled until a greater than 40% fall in expiratory flow at 30% of vital capacity from a partial flow volume manoeuvre (Vp30) was demonstrated.3 Inhaled bradykinin (0.06-8.0 mg ml-1) caused dose-related bronchoconstriction with the geometric mean cumulative dose causing a 40% fall in Vp3o (PD40) of 0.035 (95% CI: 0.02-0.07) ,umol, after placebo inhalation, which was similar to that measured before the trial (0.04: 0.02-0.09 ,umol). 4 Both nedocromil sodium (4 mg) and sodium cromoglycate (10 mg) gave significant protection (P < 0.05) against bradykinin-induced bronchoconstriction (PD40 0.37: 0.19-0.72 p,mol after nedocromil sodium and 0.22: 0.11-0.49 after sodium cromoglycate). 5 Since bradykinin-induced bronchoconstriction is probably neurally mediated we conclude that both nedocromil sodium and sodium cromoglycate have an action on neural pathways which may be useful in the control of asthma symptoms.

1. The nucleoside, adenosine, was infused into six conscious healthy male subjects at rates up to 100 micrograms kg‐1 min‐1. 2. Compared with a control 0.9% saline infusion, adenosine in all subjects caused dose dependent increases in heart rate, skin temperature and minute ventilation with corresponding falls in PaCO2, estimated transcutaneously. 3. There were no changes in systemic blood pressure, airways resistance (measured by forced partial expiratory manoeuvres), or plasma catecholamines. At the top infusion rates subjects experienced tolerable chest and abdominal discomfort. 4. These findings conflict with some previous studies in anaesthetised man and animals, in which higher doses of adenosine and its long acting analogues have caused hypotension and central respiratory depression. 5. Although some of these changes may have been due to symptoms, the cardiovascular changes may have been due to a vasodilator action and the respiratory stimulation may have been due to an action on peripheral chemoreceptors.