Sleep and Quality of Life in Allergic Rhinitis

Several growth factors (GFs) are implicated in sleep regulation. It is posited that these GFs are produced in response to neural activity and affect input-output relationships within the neural circuits where they are produced, thereby inducing a local state shift. These GFs also influence synaptic efficacy. All the GFs currently identified as sleep regulatory substances are also implicated in synaptic plasticity. Among these substances, the most extensively studied for their role in sleep regulation are interleukin-1beta (IL-1) and tumor necrosis factor alpha (TNF). Injection of IL-1 or TNF enhances non-rapid eye movement sleep (NREMS). Inhibition of either IL-1 or TNF inhibits spontaneous sleep and the sleep rebound that occurs after sleep deprivation. Stimulation of the endogenous production of IL-1 and TNF enhances NREMS. Brain levels of IL-1 and TNF correlate with sleep propensity; for example, after sleep deprivation, their levels increase. IL-1 and TNF are part of a complex biochemical cascade regulating sleep. Downstream events include nitric oxide, growth hormone releasing hormone, nerve growth factor, nuclear factor kappa B, and possibly adenosine and prostaglandins. Endogenous substances moderating the effects of IL-1 and TNF include anti-inflammatory cytokines such as IL-4, IL-10, and IL-13. Clinical conditions altering IL-1 or TNF activity are associated with changes in sleep, for example, infectious disease and sleep apnea. As our knowledge of the biochemical regulation of sleep progresses, our understanding of sleep function and of many clinical conditions will improve.

The concept, that sleep regulatory substances (sleep factors) exist, stems from classical endocrinology and is supported by positive transfer experiments in which tissue fluids obtained from sleepy or sleeping animals elicited sleep when injected into recipient animals. The transfer experiments concluded with the identification of four sleep factors: delta sleep-inducing peptide (DSIP), uridine, oxidized glutathione, and a muramyl peptide. A physiological sleep regulatory role, however, has not been determined for these substances. In contrast, transfer experiments did not play a part in the development of the strong experimental evidence that implicated the currently known sleep factors in sleep regulation. These substances include adenosine, prostaglandin D2 (PGD2), growth hormone-releasing hormone (GHRH), interleukin-1 (IL1) and tumor necrosis factor (TNF). They promote non-REMS in various species, inhibition of their action or endogenous production results in loss of spontaneous sleep, and their synthesis and/or release display variations correlating with sleep-wake activity. Although the source of these substances vary they all enhance sleep by acting in the basal forebrain/anterior hypothalamus--preoptic region. It is also characteristic of these substances that they interact in multiple ways often resulting in mutual stimulation or potentiation of each other. Finally, there is a third group of substances whose significance in sleep regulation is less clear but for which there are two or more lines of evidence suggesting that they may have a role in modulating non-REM sleep (NREMS). This group includes oleamide, cortistatin, cholecystokinin (CCK), insulin, and nitric oxide (NO). More sleep regulatory substances are likely to be discovered in the future although it is a long and difficult process requiring multiple laboratories to generate sufficient convincing data to implicate any one of them in sleep regulation.

It has long been assumed that allergic rhinitis leads to daytime sleepiness and a deterioration of nocturnal sleep, yet systematic studies have only been rarely conducted in this field. The aim of the present study was to investigate the effects of seasonal allergic rhinitis on subjective and objective sleep patterns, quality of life, and daytime sleepiness in otherwise healthy subjects in comparison with nonallergic volunteers. Twenty-five patients with seasonal allergic rhinitis and 25 healthy volunteers were enrolled in this prospective, controlled clinical trial. Daytime sleepiness and quality of life were assessed with the help of questionnaires (Epworth Sleepiness Scale, SF-36); 2 consecutive nights of fully attended polysomnography were performed before and during the pollen season of 2002. Statistically significant differences between groups were found in respect to changes in daytime sleepiness and selected parameters of quality of life. Impairment of daytime sleepiness and quality of life were related to the severity of the disease. Statistically significant differences were also found for selected parameters of the sleep studies, although the changes were only minimal, and all values were within normal ranges. Seasonal allergic rhinitis leads to increased daytime sleepiness, as well as to an impairment of quality of life, depending on the severity of the disease. Objective measurements revealed a statistically significant influence of seasonal allergic rhinitis on selected sleep parameters, but changes were not of clinical relevance. Daytime sleepiness seems to be related to the condition itself rather than to an impairment of nocturnal sleep.