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Restoration of Cough Reflex in Lung Transplant Recipients^*

^* From the Departments of Medicine (Drs. Duarte, Terminella, and Smith), Pathology (Dr. Campbell), and Surgery (Dr. Lick), University of Texas Medical Branch, Galveston, TX; the Johns Hopkins University (Dr. Myers), Bayview Hospital, Baltimore, MD.

Correspondence to: Alexander G. Duarte, MD, FCCP, Allergy, Pulmonary, Immunology, Critical Care and Sleep Medicine (APICS), University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-0561; e-mail: aduarte{at}utmb.edu

Abstract

Background: Lung transplantation involves vagal nerve interruption resulting in sensory airway denervation and impairment of the cough reflex. Following lung transplantation, it is unclear whether functional recovery of the cough reflex occurs over time. Our objective was to evaluate the afferent limb of the cough reflex in lung transplant recipients.

Methods: The assessment of cough reflex involved upper airway anesthesia, conscious sedation, and fiberoptic bronchoscopy; the biopsy forceps and a 5% dextrose solution were applied through the bronchoscope to the airway mucosa at the main carina, proximal and distal to the anastomosis. A cross-sectional group of seven subjects underwent a single assessment, while eight subjects in a longitudinal group underwent assessment at 1.5 and 12 months. Cough frequency was determined by counting the number of audible coughs and abdominal muscle contractions measured with a surface electromyogram recorder. The airway anastomosis from deceased subjects in the longitudinal group was examined for nerves.

Results: All seven subjects from the cross-sectional group demonstrated a similar cough frequency after mechanical and chemical irritation of all airway sites. All subjects in the longitudinal group who were evaluated at 1.5 weeks had a cough response at all sites except distal to the anastomosis. Twelve months after transplantation, cough was present at all sites. Immunohistochemical staining for protein gene product 9.5, low-affinity neurotrophin, and vanilloid receptors demonstrated nerves in subepithelial regions proximal and distal to the airway anastomosis.

Conclusion: In human lung transplant recipients, recovery of the cough reflex was noted 12 months after lung transplantation.

Key Words: cough • denervation • innervation • lung transplantation • neurobiology