Sleep awakens active expiration

Sleep tight

On the matter of one's respiration;

Comes a finding of pure inspiration.

To take a breath deep

At rest, fast asleep…

Flip the switch for active expiration!

Pulmonary ventilation is achieved by the repeated cyclical process of inhalation and exhalation, efficiently exchanging air between the environment and the alveoli, the highly specialized gas exchange units of the lungs. Inspiration is an active process, requiring neuromechanical coupling to generate pressure differentials within the thorax sufficient to encourage the ingress of air by bulk transfer. During quiet breathing at rest, expiration is passive, air leaving the lungs principally as a result of the relaxation of the inspiratory striated muscles of breathing and elastic recoil of the lungs. Under circumstances of increased metabolic demand however, necessitating elevated ventilation of the lungs, expiration is an active process wherein striated muscles of the abdomen are recruited in late expiration, raising intra‐abdominal pressure thereby serving as an active expiratory pump. The complementary dual pump arrangement serves to enhance minute ventilation, exemplified in response to increased chemical drive and exercise. Enhanced expiratory airflow is also critical in protective airway behaviours. Active expiration facilitates breathing by decreasing end‐expiratory lung volume and altering the length–tension relationship of the diaphragm, which both favour inspiration. It is reasoned that the dynamic range for alveolar ventilation is widened considerably by active expiration allowing tremendous scope for effective matching of ventilation to metabolism over a wide range thus ensuring homeostatic regulation of arterial blood gases and pH, in this way sub‐serving the primary function of the respiratory control network.

The neural substrate underpinning respiratory rhythm and pattern generation has proven to be complex, perhaps more so than first envisaged. Contemporary views suggest that brainstem rhythmic behaviour emerges by way of interaction between anatomically distinct independent oscillatory neural networks generating distinct phases of the respiratory cycle. Whereas activity of pre‐Bötzinger complex neurons is essential for the maintenance of ventilation, neurons of the parafacial respiratory group appear to behave as a conditional oscillator, becoming rhythmically active during expiration in periods of increased respiratory drive. In a reduced in situ rat preparation, it was recently established that hypercapnia (elevated CO₂) results in disinhibition of non‐chemosensitive late expiratory neurons of the parafacial respiratory group with coincident recruitment of abdominal nerve activity (de Britto & Moraes, 2017). In anaesthetized rats, it has been shown that excitation of parafacial respiratory group neurons promotes active expiration via cholinergic muscarinic transmission (Boutin et al. 2017). These and other observations raise intriguing questions concerning state‐dependent neuromodulatory influences on central respiratory network activity and integrative respiratory behaviour. Whereas there is some evidence in support of increased active expiration during rapid eye movement sleep, which may serve to stabilize breathing (Andrews & Pagliardini, 2015), the influence of sleep–wake state on abdominal muscle activity and its consequences for ventilation is relatively under‐studied.

In this issue of The Journal of Physiology, Leirão et al. (2018) offer new insight into the expression of active expiration during wakefulness and sleep. In freely behaving rats, diaphragm and abdominal electromyogram activities together with minute ventilation were recorded during basal breathing and sustained hypercapnic challenge. Active expiration, characterized by phasic end‐expiratory abdominal electromyogram activity, was absent during basal breathing in wakefulness and non‐rapid eye movement sleep (confirmed by electroencephalogram analysis), but was revealed recurrently during hypercapnic breathing. Abdominal muscle activity was increased and more variable during sleep compared with wakefulness, and active expiration was much more prevalent during sleep epochs, albeit presenting intermittently. Contemporaneous assessment of breathing using whole‐body plethysmography confirmed that ventilation was increased during periods of active expiration, due to increased tidal volume and shortened respiratory period.

The finding of increased active expiration during restful non‐rapid eye movement sleep is intriguing in the context of a generalized decrease in upper airway muscle activity, but not diaphragm, during sleep with relevance to obstructive airway events characteristic of obstructive sleep apnoea syndrome. The loss of tone of airway dilator muscles is generally attributed to state‐dependent disfacilitation of cranial motor outflow. The powerful sleep‐related hypotonia of upper airway muscles prevails even during increased ventilatory drive in response to hypercapnia. As such, increases in upper airway resistance, and consequential loading of breathing, may provide afferent drive awakening abdominal muscle activity during sleep. Hypoventilation may provide additional reflex‐mediated impetus to active expiration during sleep, perhaps defending against overt depression of breathing. Clearly, chemoreceptor activation during hypercapnic stress further arouses active expiration, especially during sleep, but it is curious that abdominal muscle activity presents only intermittently suggesting competing influences on parafacial respiratory group neurons (or one or more inputs), likely related to fluctuating state‐dependent neuromodulatory influences on brainstem network activity. It is also plausible however, that body posture, which affects abdominal muscle activity, influences the expression of active expiration across the sleep–wake divide, an issue difficult to address in studies of this nature. However, of note, intermittent activation of abdominal muscle activity was also reported in anaesthetized rats during rapid eye movement‐like sleep (Pagliardini et al. 2012), suggesting additional drivers of the periodic expression of active expiration.

Studies of the expiratory phase of the respiratory cycle have returned to centre stage and have never been so active! The technically challenging study of Leirão et al. (2018) offers an integrative perspective on brainstem oscillatory models of respiratory control, unmasking the pattern of abdominal muscle recruitment during respiratory challenge to reveal the mechanical consequences of such behaviour for pulmonary ventilation. In the round, studies in this exciting and important field are revealing secrets of the brainstem neural networks governing respiration, of which early pioneers could only have dreamed. In so doing, they remind us of the multi‐phased construct of the respiratory cycle and the complex manipulations of descending motor outflows that are exquisitely expressed to optimize ventilatory strategies across many behaviours, through the day and at night. Sleep tight!

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