Nonasthmatic chronic cough: No effect of treatment with an inhaled corticosteroid 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 eosinophils. 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.