Elevated tachykinin levels in induced sputum from asthmatics and cough patients with acid reflux

The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd and its licensees, to permit this article (if accepted) to be published in Thorax and any other BMJPG products and to exploit all subsidiary rights, as set out in the BMJ Publishing Group Ltd licence ABSTRACT Introduction: Acid reflux may aggravate airway disease including asthma and chronic cough. One postulated mechanism concerns a vagally mediated oesophageal-tracheobronchial reflex with airway sensory nerve activation and tachykinin release. Objective: We tested the hypothesis that patients with airways disease and reflux have elevated airway tachykinin levels compared to those without reflux. Methods: Thirty-two patients with airways disease (16 mild asthmatics and 16 non asthmatics with chronic cough) underwent 24 hour esophageal pH monitoring. Acid reflux was defined as increased total oesophageal acid exposure (% total time pH < 4 of > 4.9% at the distal probe). All subjects underwent sputum induction; differential cell counts and concentrations of substance P (SP), Neurokinin A (NKA), albumin and α2-macroglobulin were determined. Results: SP and NKA levels were significantly higher in reflux patients compared to those without (SP; 1434(680) pg/ml versus 906(593) pg/ml, p = 0.026, NKA, 81(33) pg/ml versus 52(36) pg/ml, p = 0.03). Significantly increased tachykinin levels were also measured when asthmatic patients with reflux were compared to asthmatics without, (SP; 1508 (781) pg/ml versus 737(512) pg/ml, p = 0.035, NKA; median [IQR],108 [85-120] pg/ml versus 75 [2-98] pg/ml, p = 0.02). Among asthmatics there was significant positive correlation between distal oesophageal acid exposure and SP levels (r = 0.59, p=0.01) and NKA levels (r = 0.56, p=0.02). Non-significant increases in SP and NKA were measured in coughers with reflux, (SP; 1534.71 (711) pg/ml versus 1089(606) pg/ml, p = 0.20, NKA, 56 (43) pg/ml versus 49(17) pg/ml, p = 0.71). No significant difference in differential cell counts or any other biochemical parameter was noted between study groups. Conclusion: This study demonstrates elevated airway tachykinin levels in asthmatics and cough patients with co-existent acid reflux. This suggests airway sensory nerve activation in this population.