title: CNS determinants of sleep-related worsening of airway functions: implications for nocturnal asthma.
abstract: This review summarizes the recent neuroanatomical and physiological studies that form the neural basis for the state-dependent changes in airway resistance. Here, we review only the interactions between the brain regions generating quiet (non-rapid eye movement, NREM) and active (rapid eye movement, REM) sleep stages and CNS pathways controlling cholinergic outflow to the airways. During NREM and REM sleep, bronchoconstrictive responses are heightened and conductivity of the airways is lower as compared to the waking state. The decrease in conductivity of the lower airways parallels the sleep-induced decline in the discharge of brainstem monoaminergic cell groups and GABAergic neurons of the ventrolateral periaqueductal midbrain region, all of which provide inhibitory inputs to airway-related vagal preganglionic neurons (AVPNs). Withdrawal of central inhibitory influences to AVPNs results in a shift from inhibitory to excitatory transmission that leads to an increase in airway responsiveness, cholinergic outflow to the lower airways and consequently, bronchoconstriction. In healthy subjects, these changes are clinically unnoticed. However, in patients with bronchial asthma, sleep-related alterations in lung functions are troublesome, causing intensified bronchopulmonary symptoms (nocturnal asthma), frequent arousals, decreased quality of life, and increased mortality. Unquestionably, the studies revealing neural mechanisms that underlie sleep-related alterations of airway function will provide new directions in the treatment and prevention of sleep-induced worsening of airway diseases.
authors.affiliation: Department of Physiology and Biophysics, Specialized Neuroscience Research Program, Howard University College of Medicine, 520 W. St., NW, Washington, DC 20059, USA. mhaxhiu@howard.edu
authors.forename: Musa A
authors.initials: MA
authors.lastname: Haxhiu
authors.forename: Cheryl F
authors.initials: CF
authors.lastname: Rust
authors.forename: Chevon
authors.initials: C
authors.lastname: Brooks
authors.forename: Prabha
authors.initials: P
authors.lastname: Kc
mesh_terms: D000403:Airway Resistance / Q000502:physiology*; D000818:Animals; D001249:Asthma / Q000473:pathology* / Q000503:physiopathology*; D002490:Central Nervous System / Q000473:pathology* / Q000503:physiopathology* / Q000648:ultrastructure; D002940:Circadian Rhythm / Q000502:physiology*; D006801:Humans; D008954:Models, Biological