A system configured to control pressure during cough flow of a subject, the system comprising: a subject interface configured to communicate with an airway of the subject; a pressure regulator configured to selectively control flow through the subject interface, the pressure regulator operating in (i) a first mode in which the subject interface is closed such that substantially no gas is communicated with the airway of the subject therethrough, and (ii) a second mode in which the subject interface is opened to permit gas to be exhausted from the airway of the subject through the subject interface; a controller configured to operate the pressure regulator such that during an individual exhalation of the subject, the pressure regulator is toggled between the first mode and the second mode to cause a series of exsufflation events for the individual exhalation of the subject; and a one or more gas parameter sensors, in fluid communication with the gas flowing through the subject interface, characterized in that the system further comprises a pressure relief valve associated with the subject interface and configured to: open and release gas out of the subject interface, responsive to pressure within the subject interface exceeding a predetermined threshold value while the pressure regulator operates in the first mode; and remain closed while the pressure regulator operates in the second mode, so as to maintain the pressure within the subject interface within a desired range during the cough flow. a subject interface configured to communicate with an airway of the subject; a pressure regulator configured to selectively control flow through the subject interface, the pressure regulator operating in (i) a first mode in which the subject interface is closed such that substantially no gas is communicated with the airway of the subject therethrough, and (ii) a second mode in which the subject interface is opened to permit gas to be exhausted from the airway of the subject through the subject interface; a controller configured to operate the pressure regulator such that during an individual exhalation of the subject, the pressure regulator is toggled between the first mode and the second mode to cause a series of exsufflation events for the individual exhalation of the subject; and a one or more gas parameter sensors, in fluid communication with the gas flowing through the subject interface, characterized in that the system further comprises a pressure relief valve associated with the subject interface and configured to: open and release gas out of the subject interface, responsive to pressure within the subject interface exceeding a predetermined threshold value while the pressure regulator operates in the first mode; and remain closed while the pressure regulator operates in the second mode, so as to maintain the pressure within the subject interface within a desired range during the cough flow. open and release gas out of the subject interface, responsive to pressure within the subject interface exceeding a predetermined threshold value while the pressure regulator operates in the first mode; and remain closed while the pressure regulator operates in the second mode, so as to maintain the pressure within the subject interface within a desired range during the cough flow.