A Study of the Cough Reflex in Idiopathic Pulmonary Fibrosis

Abstract

Little is known about the pathogenesis of cough in idiopathic pulmo- nary fibrosis (IPF). We hypothesized that abnormalities of respiratory tract tachykinin-containing sensory nerves may be implicated. We studied cough response to capsaicin, substance P (SP), and bradykinin in 10 healthy control subjects and 10 patients with IPF. Six patients were tested before and after steroid therapy. Induced sputum cell counts and neurotrophic factor levels were also measured in 13 pa- tients and 13 control subjects. The results show that cough sensitivity to capsaicin was greater in patients (p 0.01). Neither SP nor bradyki- nin induced cough in normal subjects. SP and bradykinin induced cough in 7/10 patients (p 0.002) and 2/10 patients (not significant) with IPF, respectively. Prednisolone caused a reduction in cough sensitivity to capsaicin (p 0.05) and SP (p 0.05) in all six patients treated. There were significantly more neutrophils (p 0.001) and higher levels of nerve growth factor (p 0.01) and brain-derived neurotrophic factor (p 0.01) in patient's sputa. These findings suggest functional upregulation of lung sensory neurones in IPF. The cough response to inhaled SP in most patients may reflect disrupted respiratory epithelium. The response to corticosteroids demonstrates that the cough is amenable to therapy. Idiopathic pulmonary fibrosis (IPF) is a condition characterized by fibroproliferation and modest mononuclear inflammation of the pulmonary interstitium. Patients typically present with wors- ening shortness of breath. However, an irritating, nonproductive cough is an additional distressing feature in 73 to 86% of cases (1, 2). Little is known about the pathogenesis of this cough, which frequently proves resistant to conventional antitussive therapies. Anecdotal evidence suggests that corticosteroids may be beneficial, but there have been no formal studies to confirm this. One previous study reported enhanced cough reflex sensitiv- ity to inhaled capsaicin in patients with IPF. By simulating a restrictive defect in normal subjects, they demonstrated that this was not due to greater deposition of aerosolized particles in proximal airways (3). This suggests there is something intrinsic to the mechanism of disease in IPF that enhances the cough reflex.