A system for enhancing secretion removal from an airway of a subject by applying a negative pressure to the airway of the subject just prior to an exsufflation is provided. The negative pressure is applied just after the subject has inhaled under his own power and/or just after generator mechanical insufflation by the system. The negative pressure applied just after inhalation/insufflation and just prior to exsufflation temporarily reduces the cross-sectional area of the airway of the subject. A reduced cross-sectional area User of the airway increases the velocity of air through the airway during a subsequent exsufflation, which results in enhanced secretion clearance. In some embodiments, the system includes one or more of a pressure generator, a subject interface, one or more sensors, a user control interface, one or more processors, and/or other components.
