Airway mucus and epithelial function in a canine model of single lung autotransplantation

Impaired mucociliary function following lung transplantation has been reported in several human and animal studies. This could be a result of altered ciliary function or mucus properties or both. We assessed airway epithelial function by means of transepithelial potential difference (PD) measurements and physical analysis of mucus. Six mongrel dogs underwent single lung autologous transplantation. Measurements were performed preoperatively and 1, 2, 4, and 10 months postoperatively. At 1 and 2 months postoperatively, there was a significant fall in PD for the transplanted, left mainstem bronchus only (-13.5 +/- 1.7 mV at 1 month and -14.6 +/- 1.7 mV at 2 months postoperatively vs -18.6 +/- 2.3 mV preoperatively, baseline; p < 0.001 for both). The PD values in the small airways, right mainstem bronchus, and the trachea remained unchanged. At 2 months postoperation, the mucus collection rate on the left side was increased (p = 0.03), while the mucus viscoelasticity was decreased (p = 0.04). By 4 months postoperation, all epithelial parameters had returned to baseline, and there was no difference in radioaerosol clearance between the two lungs. The PD decrease and alterations in secretion rate and viscoelasticity reflect disturbed epithelial functional integrity at the site of anastomosis still present at 2 months postoperation. Recovery of bronchial epithelial function and clearance in canine studies of lung autotransplantation after healing of the anastomosis area suggest that persistent impairment of lung clearance observed in some long-term human lung transplantation survivors may be due to other mechanisms such as impaired healing or epithelial function or both, during immunosuppressive therapy. Mucociliary function in the anastomosis area is compromised until complete healing ensues; we speculate that chest physiotherapy may aid in overcoming this obstacle.