Timing, Sleep, and Respiration in Health and Disease - Progress in Molecular Biology and Translational Science - page 207

to subcortical arousal as evidenced by brief EEG changes and cardiorespiratory
changes in piglets and rat pups. 187-192 This has recently been the subject of
extensive review. 132
5. IMPLICATIONS FOR HUMAN DISEASE
There are a number of diseases in which the interplay between circa-
dian regulation, sleep-wake state, and control of respiration may contribute
profoundly to the pathophysiology and associated morbidity of the disease.
These include, but are not limited to, sleep apnea, asthma, epilepsy, and sud-
den unexpected death in epilepsy (SUDEP), and SIDS. In each case, con-
tinuing to understand this interplay will undoubtedly lead to improved
preventive and therapeutic measures to ultimately reduce associated mor-
bidity and mortality from these diseases.
5.1. Sleep apnea
Perhaps the most obvious interaction between vigilance state and breathing
in human disease is seen in sleep apnea. As the name indicates, this is cessation
of airflow, or apnea, during sleep. These apneas do not occur during wake-
fulness. Sleep apnea can be obstructive, central, or mixed. In OSA, there
is cessation of airflow due to increased resistance through the airway. Most
commonly this is due to the normal decrease in excitatory input to the airway
musculature with resultant reduction in airway tone coupled with a small
airway which is easily susceptible to obstruction. Central apneas result from
loss of central input to the respiratory muscles. In some cases, there can be both
an obstructive component and a central component, termed mixed apneas.
Sleep apneas lead to arousals, either through the cessation of respiration or
through the elevation in CO 2 , or reduction in O 2 .Thearousalsserveto
increase excitatory input to the airway muscles thereby improving airway
tone and patency and allow resumption of normal breathing. The return of
breathing to normal corrects the blood gas aberration. If these are not
corrected, the CO 2 will become too high and respiratory drive will be lost.
While the arousals ultimately serve to maintain respiratory drive, recurrent
sleep disruption leads to excessive daytime sleepiness and contributes pro-
foundly to the morbidity associatedwith sleep apnea. Many patients with sleep
apnea can be treated with a conceptually simple maneuver in which contin-
uous positive pressure is delivered to their airway to maintain its patency and
greatly reduce the number of nighttime apneas. While there is clearly an asso-
ciation between apnea and sleep, there may also be a circadian component. 193