Hypertonic saline alters ion transport across the human airway epithelium

Aerosolized hypertonic saline is currently being investigated as a new agen t for the treatment of impaired mucociliary clearance which occurs in many respiratory diseases, Mannitol aerosols, in particular dry powder inhalers, have been proposed as an alternative treatment to saline, offering the sam e osmotic load with other benefits. However, the effects of these hypertoni c aerosols on airway epithelial ion transport processes have not been teste d in human subjects in vivo. This report examines the effect of these solut ions on airway ion transport using the nasal potential difference (PD) tech nique, Seven healthy nonsmoking adult volunteers were studied. On different days, a dose-response curve was constructed for the saline added to Krebs N-[2-hy droxyethyl] piperazine-N'-[2-ethanesulphonic acid] (HEPES) diluent, The rev ersibility of this saline effect was measured, and the response to addition al saline (500 mM) and mannitol (1 M) compared, Hypertonic saline decreased nasal PD in a dose-related manner, with mean (S EM) decreases in PD (less negative) of 6.6 (1.5), 7.6 (1,6), 10.0 (2.0), 13 .1 (2.9) and 14.8 (3.2) mV (n = 4) for addition of 150 mM, 250 mM, 500 mM, 1,200 mM and 2,000 mM NaCl to the Krebs HEPES diluent, respectively. The ef fect of hypertonic saline was fully reversible with washout for 3 min (pres aline 15.9 (0.5) mV, postwashout 15.8 (1.1) mV, (n = 4)). The hypertonic sa line response was rapid in onset, sustained for at least 4 min, and decreas ed PD from 13.7 (1.7) mV to 5.1 (1.3) mV (n = 7, p < 0.001), In contrast, a ddition of mannitol to the perfusate did not significantly alter nasal PD,, vith a nonsignificant trend towards an increase (more negative) in the PD, (premannitol 13.9 (1.6) mV, postmannitol 15.3 (2.0) mV, n = 7), As the osmotic stimulus of the 1 M mannitol is similar to that of the 500 m M sodium chloride, the divergent nasal potential difference responses sugge st that the response to the saline was specific to the sodium chloride itse lf and not the simultaneous change in osmolarity. This demonstrates that th e human airway epithelium irt vivo can respond to topical hypertonic saline independent of the altered osmolarity.