| Biography | |
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 Prof. Lu-Yuan Lee University of Kentucky, USA |
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| Title: Role of TRPV1 as a trigger of acute bronchoconstriction in asthma: from ion channel to patient | |
| Abstract: Transient receptor potential vanilloid type 1 receptor (TRPV1) is a nonselective cation channel and a polymodal transducer. In the respiratory tract, it is expressed predominantly in non-myelinated (C-fiber) sensory nerves. Stimulation of these TRPV1-expressing sensory endings is known to elicit reflex responses such as cough and reflex bronchoconstriction. Increasing evidence suggests that activation of TRPV1 plays an important part in the manifestation of various symptoms of airway hypersensitivity associated with airway inflammatory diseases. Indeed, allergen sensitizationinduced airway inflammation markedly enhanced the expression of TRPV1 and the sensitivity of pulmonary C-fiber afferents in an animal model of asthma. Recent studies in our laboratory have shown a considerably lower temperature threshold for activating TRPV1 expressed in pulmonary sensory nerves. Increasing temperature to ~39°C significantly elevated the baseline activity and sensitivity of isolated rat vagal pulmonary sensory neurons, and an involvement of TRPV1 was primarily responsible. Furthermore, a brief isocapnic hyperventilation (at ~40% of maximum voluntary ventilation) of humidified warm air triggered an immediate increase in airway resistance (Raw) and coughs in patients with mild and stable asthma. In sharp contrast, the same challenge failed to evoke any significant change in Raw or cough in healthy individuals. Pretreatment with ipratropium bromide completely prevented the bronchoconstriction in the asthmatic patients, but did not abolish the cough response, indicating an involvement of airway sensory nerves and cholinergic reflex. Hyperventilation of humidified air at room temperature did not cause bronchoconstriction or cough in the same patients. In conclusion, increasing airway temperature stimulated airway sensory nerves, presumably via an activation of TRPV1, and elicited both cough and cholinergic reflex bronchoconstriction in patients with mild asthma. These results further suggest that the sensitivity of TRPV1-expressing sensory nerves is upregulated in asthmatic airways. (Supported in part by National Institute of Health grants AI123832, HL96914 and UL1TR001998) | |
| Biography: Dr. Lu-Yuan Lee is Fred Zechman Professor of Physiology and Biomedical Engineering at the University of Kentucky. His current research focuses on the underlying mechanisms of bronchial hypersensitivity associated with airway inflammatory diseases. He has published over 170 papers, including 35 invited reviews and book chapters (Google Scholar h-index of 41). He is the recipient of several research and teaching awards, serves as a member of the review panels for national and international research organizations/foundations including the National Institute of Health, and editorial boards of several major journals. He was elected as a Fellow of the American Physiological Society and the Biomedical Engineering Society. | |
