Mechanistically, this scenario likely reflects the fact that the hypertonic saline results in a high salt concentration on airway surfaces, which in turn generates a gradient of Cl− to be absorbed through the partially functional CFTR-mediated channel and the paracellular pathway, together with the absorption of Na+ by ENaC and the paracellular pathway, and these thus may limit the sustainability of osmotic effects on the surfaces of COPD normal airways. The gene discussed is CFTR; the disease is chronic obstructive pulmonary disease.