The endogenous circadian system worsens asthma at night independent of sleep and other daily behavioral or environmental cycles.
asthma
bronchodilation
circadian misalignment
circadian rhythms
sleep
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
14 09 2021
14 09 2021
Historique:
accepted:
14
07
2021
received:
19
07
2021
entrez:
8
9
2021
pubmed:
9
9
2021
medline:
15
12
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34493686
pii: 2018486118
doi: 10.1073/pnas.2018486118
pmc: PMC8449316
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR002541
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL064815
Pays : United States
Organisme : NCRR NIH HHS
ID : M01 RR002635
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL118601
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL155681
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL134632
Pays : United States
Informations de copyright
Copyright © 2021 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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