Nonasthmatic Chronic Cough: No Effect of Treatment with an Inhaled Corticosteriod in Patients without Sputum Eosinophilia

Abstract

BACKGROUND: Inhaled corticosteroids are effective in suppressing a chronic cough without asthma associated with sputum eosinophilia.OBJECTIVE: To investigate the inflammatory characteristics in the induced sputum of patients with a chronic cough without asthma or known cause and the effects of budesonide treatment on chronic cough in those patients.PATIENTS AND METHODS: Forty-four adults (mean [minimum, maximum] age of 45 years [20,75], 28 women, 17 atopic subjects and 32 nonsmokers]), with a daily bothersome cough for at least one year and who had no evidence of asthma or other known cause for the cough, were consecutively enrolled. The trial was a randomized, double-blind, controlled parallel group trial of budesonide 400 mg twice daily for two weeks versus placebo. Patients then received open administration of the same dose of budesonide for a further two weeks. Sputum was induced before and at the end of each treatment period. Cough severity was documented by a visual analogue scale.RESULTS: Thirty-nine (89%) patients produced mucoid sputum after induction on at least one study visit. At baseline, the majority (59%) had a mild elevation in the median proportion of neutrophils (65%). All had elevated fluid phase levels of fibrinogen (3200 µg/L) and albumin (880 µg/L), and high levels of interleukin-8 and substance P. Interleukin-8 correlated with neutrophils (rho=0.72, P<0.001), fibrinogen (rho=0.65, P<0.001), albumin (rho=0.67, P=0.001) and eosinophil cationic protein (rho=0.60, P=0.001). Substance P correlated with albumin (rho=0.60, P=0.006). No subject had an increase in eosino-phils. Treatment with budesonide did not affect cough or sputum measurements.CONCLUSIONS: Patients with nonasthmatic chronic cough enrolled in this study had evidence of a mild neutrophilia and/or microvascular leakage. Chronic cough did not respond to treatment with budesonide, perhaps because the cause was not associated with sputum eosinophilia.