The endogenous circadian system worsens asthma at night independent of sleep and other daily behavioral or environmental cycles
| Autor: | Frank A.J.L. Scheer, Heather Evoniuk, Steven Shea, Elliot Israel, Sally A Shiels, Michael F. Hilton, Rena Sugarbaker, R. Timothy Ayers, Anthony F. Massaro, Atul Malhotra |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Exacerbation Physiology medicine.drug_class bronchodilation Environment Nocturnal Young Adult Bronchodilator medicine Humans Circadian rhythm sleep Asthma Behavior Multidisciplinary business.industry circadian misalignment Biological Sciences asthma medicine.disease Sleep in non-human animals Circadian Rhythm circadian rhythms Case-Control Studies Ambulatory Female Wakefulness business |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2018486118 |
| Popis: | Significance For centuries, it has been recognized that asthma severity shows a daily rhythm, with the worst symptoms at night. However, it is unclear to what degree this is driven by everyday behaviors, such as sleep, physical activity, and body posture changes, versus intrinsic rhythms generated by the internal body clock (i.e., the circadian system). To distinguish the contribution of the circadian system, patients with asthma underwent two complementary gold-standard circadian protocols: a constant routine and a forced desynchrony protocol. These highly standardized protocols revealed that the endogenous circadian system plays a significant role in modulating pulmonary function and asthma severity independent of sleep and other daily behavioral or environmental cycles. Moreover, these circadian influences summate with daily behavioral and environmental effects to drive asthma to be worst at night. Asthma often worsens at night. To determine if the endogenous circadian system contributes to the nocturnal worsening of asthma, independent of sleep and other behavioral and environmental day/night cycles, we studied patients with asthma (without steroid use) over 3 wk in an ambulatory setting (with combined circadian, environmental, and behavioral effects) and across the circadian cycle in two complementary laboratory protocols performed in dim light, which separated circadian from environmental and behavioral effects: 1) a 38-h “constant routine,” with continuous wakefulness, constant posture, 2-hourly isocaloric snacks, and 2) a 196-h “forced desynchrony” incorporating seven identical recurring 28-h sleep/wake cycles with all behaviors evenly scheduled across the circadian cycle. Indices of pulmonary function varied across the day in the ambulatory setting, and both laboratory protocols revealed significant circadian rhythms, with lowest function during the biological night, around 4:00 AM, uncovering a nocturnal exacerbation of asthma usually unnoticed or hidden by the presence of sleep. We also discovered a circadian rhythm in symptom-based rescue bronchodilator use (β2-adrenergic agonist inhaler) whereby inhaler use was four times more likely during the circadian night than day. There were additive influences on asthma from the circadian system plus sleep and other behavioral or environmental effects. Individuals with the lowest average pulmonary function tended to have the largest daily circadian variations and the largest behavioral cycle effects on asthma. When sleep was modeled to occur at night, the summed circadian, behavioral/environmental cycle effects almost perfectly matched the ambulatory data. Thus, the circadian system contributes to the common nocturnal worsening of asthma, implying that internal biological time should be considered for optimal therapy. |
| Databáze: | OpenAIRE |
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