Little is known about the pathogenesis of cough in idiopathic pulmonary 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 patients and 13 control subjects. The results show that cough sensitivity to capsaicin was greater in patients (p < 0.01). Neither SP nor bradykinin 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.

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The natural occurrence of cyclic nucleotides in higher plants, formerly a topic of fierce debate, is now established, as is the presence of nucleotidyl cyclases and cyclic nucleotide phosphodiesterases capable of their synthesis and breakdown. Here we describe the significant properties of cyclic nucleotides, also outlining their second messenger functions and the history of plant cyclic nucleotide research over its first three decades. Findings of the last five years are detailed within the context of the functional role of cyclic nucleotides in higher plants, with particular emphasis upon nucleotidyl cyclases and cyclic nucleotide-responsive protein kinases, -binding proteins and -gated ion channels, with future objectives and strategies discussed.