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Updated: Jun 24, 2026

Establishment of a Mouse Model with Cough Hypersensitivity via Inhalation of Citric Acid
Published on: January 10, 2025
The citric acid cough threshold and the ventilatory response to carbon dioxide on ascent to high altitude
A A Roger Thompson1, J Kenneth Baillie, Matthew G D Bates
1Academic Unit of Respiratory Medicine, University of Sheffield, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK. r.thompson@sheffield.ac.uk
Abstract:
Ventilatory control undergoes profound changes on ascent to high altitude. We hypothesized that the fall in citric acid cough threshold seen on ascent to altitude is mediated by changes in the central control of cough and would parallel changes in central ventilatory control assessed by the hypercapnic ventilatory response (HCVR). Twenty-five healthy volunteers underwent measurements of HCVR and citric acid sensitivity at sea level and during a 9 day sojourn at 5200m. None of the subjects had any evidence of respiratory infection. Citric acid cough threshold fell significantly on ascent to 5200m. The slope, S, of the HCVR increased significantly on ascent to 5200m and during the stay at altitude. There was no correlation between citric acid sensitivity and HCVR. We conclude that the change in citric acid cough threshold seen on exposure to hypobaric hypoxia is unlikely to be mediated by changes in the central control of cough. Sensitivity to citric acid may be due to early subclinical pulmonary edema stimulating airway sensory nerve endings.
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