Sleep Apnea and Chronobiology - Advances in Medical Science

By Admin

The chronobiological aspects of sleep disorders such as obstructive sleep apnea have gained increasing scientific attention in recent years, both in the U.S. and abroad. Studies have shown that in addition to regulating the sleep-wake cycle, circadian systems play an important role in the development of respiratory events during the night, a delicate balance that can be very easily disrupted by sleep disorder symptoms. In addition, inflammatory markers that demonstrate circadian changes are often seen among patients with sleep apnea and other sleep-related breathing disorders, leading to further investigations of the mechanisms by which these symptoms impinge upon circadian clock functions and cause dysregulation. While further research is needed to illuminate the full effects of these internal timing systems, much has been learned about how their disruption can lead to the onset and development of disease, including obstructive sleep apnea (OSA), central sleep apnea (CSA), and chronic obstructive pulmonary disease (COPD). Continued research in these areas could potentially provide new and more effective therapeutic targets for the treatment and maintenance of sleep disordered breathing, an approach that takes into account the individual needs of personal chronotypes as part of a larger picture of long-term health and wellbeing.

What Are Circadian Rhythms?

Circadian rhythms are a collection of internally driven biochemical and physiological processes that fluctuate in a 24-hour cycle and can be conditioned by external cues. In recent years these processes have helped to guide effective, time-managed advances in the treatment of disease. For most people, energy and immune potential are highest during the day hours before and after the post-lunch slump. These times can vary for night owls or early morning people, but consistent sleep will have a major effect on the fluctuations. If you’re sleep deprived, the energy losses at night and midday will feel extreme and even life-changing. On the other hand, when you’re caught up on sleep, the fluctuations in energy will feel less significant and you will feel more balanced throughout the day.

The Chronobiology of Disease

For sleep-related breathing disorders (SRBD) in particular, the misalignment of circadian rhythms often results in adverse consequences, and at the same time, therapy directed toward the entrainment of healthy circadian rhythms often results in increased positive outcomes. These findings have been corroborated through multiple studies on a variety of focus areas including circadian factors in blood pressure, sympathetic activity, corticoid biogenesis, and overall metabolism, all of which are severely altered in patients with sleep disordered breathing, especially in the case of OSA. As these disorders progress, response to the threat of hypoxia causes additional problems that can manifest in a number of different comorbid conditions. Studies have found, for example, that hypoxia-inducible transcription factors interact with core circadian clock transcription factors to disrupt the cardiopulmonary system that regulates blood flow, heart rate, and breathing. This is known as molecular crosstalk, and when detected it can help medical experts develop alternative therapeutic strategies such as chronotherapy to address symptoms when they are most severe, for example, when these disease-specific biomarkers are most present in the system. While the interplay between these complex pathways has not yet been fully elucidated, the rhythmic cycles of chromobiological response mechanisms are easily recognized, and therefore used as both a diagnostic measure and a means of determining effective treatments. In OSA, apnea-hypopnea index (AHI) readings and oxygen desaturation levels are both affected by chronobiology. AHI readings are highest in the biological day, while desaturation occurs with more regularity and severity during the biological night. Research in this area has found that apnea-hypopnea events tend to occur during non-REM sleep stages, particularly during morning sleep, which corresponds with circadian-driven changes in pulmonary function. This is also true of napping, when patients are susceptible to apnea symptoms due to potential disruption in the sleep-wake cycle. Desaturation, on the other hand, tends to occur after several sleep cycles have passed, often during the deeper sleep stages of the late-night hours. This coincides with prolonged, gradual breathing changes that often develop into apnea events over time. It also explains variability in the body’s immune responses. Any deprivation of natural circadian sleep patterns will affect the severity of immune response, and therefore affect the overall health of the patient.

Chronotherapy

Chronotherapy is a behavioral technique involving the scheduling of prescribed treatments according to specific stages in the circadian cycle. When sleep deprivation is an issue, bedtimes are often systematically delayed to follow the natural tendency of human biology. For those using PAP therapy, this may also include specified timing for therapy sessions. For others, it may require the use of auto-titrating capabilities for real-time therapy adjustments during the night. The closer one is able to time therapy sessions according to sleep-wake intervals, the easier it becomes to minimize side effects and maximize benefits. Starting therapy as late as possible, for example, can help ensure that sessions include early morning hours when patients are most vulnerable to symptoms. Since PAP-therapy compliance is defined as four hours on most nights, some patients may end therapy sessions before the onset of symptoms. Unfortunately, this is not uncommon, especially for new patients who find themselves removing the mask in their sleep, or when only slightly awake. The goal of chronotherapy is to ensure that treatments are timed to correspond with the rhythms of the disease. Chronotherapeutic approaches have the potential to bridge many gaps in sleep and medical science, combining biochemical, physiological, pharmacological, and respiratory care approaches to address the overall impact of disease and the effectiveness of therapies. Thus far, the clinical translation of chronotherapy to the treatment of sleep disorders such as OSA has resulted in such significant benefits for patients that it is now being incorporated in a broad range of clinical and home-care applications.The importance of timing in medicine is nothing new, but the science of assessing circadian changes in order to optimize treatment results is something that continues to show promise in the health outcomes of patients.