ABNORMAL INTRAEPITHELIAL AIRWAY NERVES IN PERSISTENT UNEXPLAINED COUGH

Idiopathic persistent nonproductive cough (PNPC) is characterized by e nhanced cough sensitivity to inhaled capsaicin, suggesting that capsai cin-sensitive afferent airway nerves are either present in increased n umbers or functionally upregulated. In 16 patients with idiopathic PNP C and eight healthy control subjects, we measured cough sensitivity to inhaled capsaicin and the anatomic density in bronchial epithelium of nerves immunoreactive for the general nerve-marker protein gene produ ct (PGP)-9.5 and the sensory neuropeptides calcitonin-gene-related-pep tide (CGRP) and substance-P (SP). The log concentrations of capsaicin required to elicit at least two (C2) and five (C5) coughs were signifi cantly lower in patients (P) than in control subjects (C) (median [ran ge] log C2, P = 0.3 [-0.3 to 1.2] mu M; C = 1.5 [0.9 to 2.1], p < 0.00 05; log C5, P = 0.8 [-0.3 to 2.1]; C = 2.6 [1.8 to 3.0], p < 0.0005). In bronchial epithelium taken from the carina of the right upper lobe (RUL) and a subsegmental carina of the right lower lobe (RLL), total n erve density (PGP-9.5 immunoreactivity) was greater in P than C, altho ugh this was not significant. CGRP-immunoreactive nerve density was si gnificantly higher in P than in C in the RUL (median [range] P = 1.05% [0.13 to 5.08]; C = 0.02% [0 to 0.24], p = 0.001) and RLL (P = 0.59% [0.04 to 3.14]; C = 0% [0 to 0.50], p < 0.02). SP-immunoreactive nerve s were not significantly different in the two groups. Abnormal intraep ithelial airway nerves containing increased quantities of CGRP are pre sent in patients with idiopathic PNPC. This abnormality may underlie t he enhanced cough sensitivity to inhaled capsaicin that is seen in the se patients.