Expiration: breathing's other face.

The evolution of the aspiration pump seen in tetrapod vertebrates from the buccal-pharyngeal force pump seen in air breathing fish and amphibians appears to have first involved the production of active expiration. Active inspiration arose later. This appears to have involved reconfiguration of a parafacial oscillator (now the parafacial respiratory group/retrotrapezoid nucleus (pFRG/RTN)) to produce active expiration, followed by reconfiguration of a paravagal oscillator (now the preBötC) to produce active inspiration. In the ancestral breathing cycle, inspiration follows expiration, which is in turn followed by glottal closure and breath holding. When both rhythms are expressed, as they are in reptiles and birds, and mammals under conditions of elevated respiratory drive, the pFRG/RTN appears to initiate the respiratory cycle. We propose that the coordinated output of this system is a ventilation cycle characterized by four phases. In reptiles, these consist of active inspiration (I), glottal closure (E1), a pause (an apnea or breath hold) (E2), and an active expiration (E3) that initiates the next cycle. In mammals under resting conditions, active expiration (E3) is suppressed and inspiration (I) is followed by airway constriction and diaphragmatic braking (E1) (rather than glottal closure) and a short pause at end-expiration (E2). As respiratory drive increases in mammals, expiratory muscle activity appears. Frequently, it first appears immediately preceding inspiration (E3) just as it does in reptiles. It can also appear in E1, however, and it is not yet clear what mechanisms underlie when and where in the cycle it appears. This may reflect whether the active expiration is recruited to enhance tidal volume, increase breathing frequency, or both.