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Causes and outcome in cough

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1N. Yousaf, 1S. Matos, 2S. S. Birring, 1I. D. Pavord. 1Glenfield Hospital, Leicester, Leicester, UK, 2Kings College Hospital, London, UK

Introduction Unexplained chronic cough is a common condition with no satisfactory treatments. We have previously shown that the induced sputum neutrophil count is independently associated with cough frequency and have speculated that cough is causally linked to neutrophilic airway inflammation. Long-term, low dose macrolide antibiotics reduce neutrophilic airway inflammation in other inflammatory airway diseases. We tested the hypothesis that long-term low dose erythromycin reduces the induced sputum neutrophil count and 24 h cough frequency in patients with unexplained chronic cough.

Methods Thirty patients with an unexplained chronic cough lasting >8 weeks were randomised to take 250 mg of erythromycin once daily (n = 15) or placebo (n = 15) for 12 weeks in a double-blind parallel group study. 24 h ambulatory cough frequency, the concentration of inhaled capsaicin required to cause two (C2) and five (C5) coughs, the induced sputum neutrophil count, the Leicester Cough Questionnaire (LCQ) and a 100 mm cough visual analogue score (VAS) were measured before and 6, 12 and 24 weeks after the start of treatment. The primary outcome measure was change in 24 h cough frequency at 12 weeks.

Results 24 h cough frequency at baseline and 12 weeks was 353 and 243 (mean fold difference 1.45, 95% CI 1.02 to 2.17) with erythromycin, and 536 and 390 (mean fold difference 1.37, 95% CI 1.15 to 1.64) with placebo. There was no significant difference in the change in cough frequency between the groups at 12 weeks (mean difference in change 0.94, 95% CI 0.63 to 1.41, p = 0.585) or at other times. The induced sputum neutrophil count reduced significantly from 67.8% to 56.6% after 12 weeks treatment with erythromycin and there was a significant between-treatment difference in the change in percentage sputum neutrophils at 12 weeks (−10.2 vs +6.6; mean difference 18.8; 95% C I 1.6 to 32.1, p = 0.03) but not at other times. There was no difference in the change in LCQ, cough VAS, C2 and C5 between treatments.

Conclusion Treatment with low dose erythromycin for 3 months does not reduce cough frequency in patients with unexplained chronic cough despite significantly reducing neutrophilic airway inflammation.

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