Timing, Sleep, and Respiration in Health and Disease - Progress in Molecular Biology and Translational Science - page 198

pressure (tension) status to detect changes. The balance between volume and
pressure is sent to higher centers as “length-tension appropriateness.” 81 Any
aberration in this system leads to adjustments in medullary respiratory motor
activity. 82 In addition to mechanoreceptors, there are irritant receptors
within the respiratory tract that are activated by various exogenous stimuli
(e.g., dust, etc.) and send afferent to higher centers to typically induce a
cough.

3. CIRCADIAN RHYTHMS AND BREATHING
3.1. Circadian regulation of breathing
All organisms display circadian rhythms. 83 In mammals, these rhythms are
governed by the master oscillator in the paired suprachiasmatic nuclei
(SCN) of the anterolateral hypothalamus. 84,85 The master SCN oscillator
drives rhythms in other regions, both central and peripheral. 86 Conse-
quently, the SCN regulates a variety of behavioral and physiological pro-
cesses in a near 24-h pattern. Among these is breathing. 87
Respiratory function in humans is typically assessed with spirometry in
which a subject inspires maximally and then expires as quickly and
completely as possible. Measurements obtained in this manner include total
lung capacity, forced vital capacity (FVC), tidal volume ( V T ), residual vol-
ume, forced expiratory volume in one second (FEV 1 ), forced expiratory
flow, peak expiratory flow (PEF), and FEV 1 /FVC (a more patient-specific
indicator of airway tone). In addition, RR can be counted manually or mea-
sured along with V T via plethysmography. These measures are used together
to determine minute ventilation ( V E ), the functional volume of air moved
through the lungs in one minute. and P O 2 can be measured via opti-

cal or electrochemical sensors or directly in the serum along with pH in an
arterial blood gas assay. Finally, the respiratory responses to manipulations
including chemical stimulation with hypoxia and hypercapnia (i.e., the hyp-
oxic and hypercapnic ventilator responses, respectively) can be measured.
Through a variety of studies in a wide range of species including humans, 88
non-human primates, 89 dogs, 90 rats, 91 mice, 92 d ucks, 93 snakes, 94 cows, 95 and
even worm s 96 and bees, 97 it has been shown that many respiratory measures
can be subject to circadian regulation, though this varies greatly, depending on
the species and experimental conditions. 98
In one study of 30 male subjects, robust circadian variation was seen in
V T , V E , and V T / T I . These participants were subjected to a constant routine

ð P CO 2 Þ