SummaryStimulation of exposed C‐fibre afferent nerve endings by inflammatory mediators may contribute to airway inflammation and bronchoconstriction in asthma through the release of neuropathies from collateral nerve endings. The polar opioid peptide 443c81 is a μ‐optoid receptor agonist which inhibits C‐libre activation and non‐echolinergie neurally mediated bronchoconstriction in animal models. We have compared the effect of 443c81 (5 ml of 1 4 mg ml solution nebulited) four times daily for 7 days with placebo on asthma control in a double‐blind parallel group study of 40 subjects with mild asthma. Twenty subjects (12 male, mean FEV, 83 Predicted) received placebo and 20 (15 male, mean FEV, 91, predieted) 443e81 after a 1 week run‐in Efficacy was assessed by comparing changes from baseline values in FEV1provocative dose of histamine causing a 20, fall in FEV1(PD20), symptom scores, bronchodilator use and home peak flow readings 443c81 had no acute effect on FEV1and the mean changes in FEV1 after 1 week of treatment were not significantly different placebo 0.9. 443c81 3.8. One hour after the first dose of 443c81 PD20 mecreased from a geometric mean of 0.88 to 1.48 μmol (mean change 0.76 doubling doses: 95 CI 0.23. 1.29) but this did not differ significantly from the change with placebo (mean difference between 443c81 and placebo 0.63 doubling doses. 95. CI −0.2. 1.5:P− 0.095). After 1 week's treatmentPD20 was similar to baseline values with 443c81 (0.78 μmol) and placebo (baseline 0.71. post‐treatment 0.93 μmol) Symptom scores including cough scores.) bronehodilator use and peak flow recordings did not change significantly during or following treatment with 443c81 compared with placebo. There were no important adverse events. The lack of effect of 443c81 in our study would not support a role for activation
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