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BackgroundPatients with some neuronal hypersensitivity syndromes experience increased autonomic symptoms. Chronic cough is thought to be a neuronal hypersensitivity disorder and, therefore, may be associated with increased autonomic symptoms.Methods96 chronic cough subjects were recruited from the tertiary cough clinic based at Wythenshawe Hospital, Manchester, UK; 76 healthy controls were also recruited. Subjects were aged >18 years. Those with significant respiratory disease, significant smoking history or taking medication known to affect cough or autonomic function were excluded. Subjects completed the Composite Autonomic Symptom Score (COMPASS) 31 autonomic symptom questionnaire, the Cough Quality of Life Questionnaire (CQLQ) and a cough severity visual analogue scale (VAS).Results96 chronic cough subjects and 76 healthy volunteers were included in the final analysis. Mann–Whitney U-tests comparing COMPASS 31 scores in both groups showed that the total COMPASS 31 score was significantly higher in the patient group (median 18.4, interquartile range (IQR) 7.5–32.0) than the control group (median 3.6, IQR 1.1–9.5; p<0.001). The chronic cough subjects had significantly higher symptom scores than the healthy volunteer groups in all domains (p≤0.001) except vasomotor symptoms (p=0.770). There was a positive association between COMPASS 31 and CQLQ in the patient group (p<0.001, r=0.432) but not COMPASS 31 and VAS (p=0.227).InterpretationChronic cough patients do indeed report more frequent and severe autonomic symptoms than healthy volunteers, indicating that this population may suffer from dysautonomia. At present, it remains unclear whether this occurs as a result of the cough or whether both the cough and dysfunction are part of some wider vagal pathology.

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Introduction and ObjectivesPatients with chronic cough complain of a variety of sensations that they perceive as provoking coughing, identifying irritation, tickle and the urge to cough (UTC) as important. Effective therapies for chronic cough such as low dose morphine have failed to reduce experimentally evoked cough responses, but their effect on the sensations driving cough is unknown. We hypothesised that low dose morphine therapy reduces the sensations driving cough and predicted that the sensations experienced during inhalational cough challenge may demonstrate this mechanism.MethodsTwenty-two refractory chronic cough patients (mean age 61.7 years, 18 female, mean cough duration 14 years) taking low dose morphine sulphate treatment enrolled into a double-blind randomised controlled crossover trial comparing the effects of low dose morphine sulphate with matched placebo. Following withdrawal of their morphine therapy, participants were randomised to receive morphine (5–10 mg BD slow release) or matched placebo during two treatment period (5–7 days duration) separated by a 5–7 day washout. On the final day of each treatment period subjects inhaled increasing concentrations of citric acid (0.01–4 M, 18 ascending concentrations), rating irritation, tickle, UTC and taste on 100 mm visual analogue scales (VAS; 0 mm=none and 100 mm=worst) after each inhalation. The challenge continued until subjects coughed at least twice on any concentration of citric acid (C2). For the analysis, general estimating equation (GEE) models evaluated the effect of treatment on reported sensations, with increasing per citric acid dose.ResultsCompared with placebo, low dose morphine significantly reduced the VAS scores for tickle and irritation during the citric acid challenge (p=0.021, p=0.039), however UTC, taste and the number of coughs evoked were not improved (p=0.105, p=0.167, and p=0.337). Of particular note, morphine had no significant impact on C2 compared with placebo (p=0.611).ConclusionsThis data shows that treatment with low dose morphine significantly reduces the noxious sensations driving cough. The effects on tickle and irritation appear more important than any impact on the UTC, numbers of coughs triggered or the traditional C2 endpoint, suggesting that reducing somatic sensations may be an important component of the mode of action of opioids in the treatment of cough.Abstract P104 Figure 1Figure showing the effects of morphine and placebo on noxious sensations (A “Irritation” B “tickle”) evoked by increasing doses of citric acid in our cough challenge *p < 0.05.

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