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(Chest. 2003;124:306-313.)
© 2003 American College of Chest Physicians

Hyperosmolar Solutions Stimulate Mucus Secretion in the Ferret Trachea*

Chikako Kishioka, MD, PhD; Kosuke Okamoto, MD, PhD; Jung-Soo Kim, MD, PhD and Bruce K. Rubin, MD, FCCP

* From the Department of Otolaryngology (Drs. Kishioka and Okamoto), Mie University School of Medicine, Tsu, Mie, Japan; and Wake Forest University School of Medicine (Drs. Kim and Rubin), Winston-Salem, NC.

Correspondence to: Bruce K. Rubin, MD, FCCP, Professor and Vice-Chair, Department of Pediatrics, Professor of Medical Engineering, Medicine, Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1081; e-mail: brubin{at}wfubmc.edu

Study objectives: Inhalation of hypertonic saline or mannitol solutions acutely increases mucociliary clearance. Because increased clearance is often coupled with increased mucus secretion, we hypothesized that hyperosmolar agents would stimulate mucus secretion.

Setting and subjects: The isolated tracheae of healthy young adult ferrets were studied in a basic research laboratory.

Measurements and results: We demonstrated that there was a dose-dependent increase in mucin secretion by enzyme-linked lectin assay after incubation with 1.69 g/dL (597 mOsm/L), 3.69 g/dL (1,192 mOsm/L), 5.69 g/dL (1,823 mOsm/L), and 10.69 g/dL (3,612 mOsm/L) of saline solution over Krebs-Henseleit solution control (288 mOsm/L) [p < 0.01 for 1.69 g/dL of saline solution and p < 0.0001 for others]. Mannitol solution, 15 g/dL (1,040 mOsm/L), also significantly increased mucin secretion (n = 4, p < 0.005). There was a 47% and 54% increase in secretion of the serous cell product lysozyme after exposure to 3.69 g/dL (1,192 mOsm/L) and 10.69 g/dL (3,612 mOsm/L) saline solutions, respectively (n = 5, p < 0.05). Secretion was only stimulated when the hyperosmolar exposure was on the luminal side of the epithelium. Mucin secretion was induced within minutes of 3.69 g/dL of saline solution exposure, and this increased mucin secretion quickly peaked. The ratio of mucin to lysozyme secretion was approximately 2. This ratio appeared to be independent of the osmotic concentration of the stimulus and therefore of secretory rate.

Conclusions: Mucus secretion is markedly stimulated in response to hyperosmolarity. This may be a protective response. These results also suggest that the therapeutic use of hyperosmolar aerosols should be evaluated with care when used for patients with mucus hypersecretion and impaired mucus clearance.

Key Words: hypertonic saline solution • inhalation administration • mucus • mucociliary clearance






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