Disturbed circadian rhythm in ICU patients as indicated by melatonin levels: a prospective pilot study

Kiss, K.; Földesi, Imre; Kemény, Lajos; Csernus, Valér; Molnár, Z.; Singer, Joseph

doi:10.1186/cc14629

Cited by 2 publications

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“…Thus, several groups have hypothesized that patients in intensive care are likely to have disrupted molecular clocks and this disruption may, in theory, compound the existing immune and metabolic insults ( Telias and Wilcox, 2019 ; Jobanputra et al, 2020 ; Haspel et al, 2021 ). Initial studies have demonstrated disruption of sleep/wake and core-body temperature rhythms ( Gazendam et al, 2013 ) among IC patients and absent or altered circadian patterns of serum melatonin and cortisol ( Mundigler et al, 2002 ; Kiss et al, 2015 ; Maas et al, 2020b ). Similar results have been obtained when comparing the temporal patterns in whole blood gene expression among IC patient cohorts and controls, both at the level of select core clock genes ( Diaz et al, 2020 ) and the larger transcriptome ( Maas et al, 2020a ).…”

Section: Introductionmentioning

confidence: 99%

Multi-tissue transcriptional changes and core circadian clock disruption following intensive care

2022

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Objective: Both critical illness and current care have been hypothesized to upset daily rhythms and impair molecular circadian function. However, the influence of critical illness on clock function in different tissues and on circadian output genes are unknown. Here we evaluate the effect of critical care and illness on transcription, focusing on the functional organization of the core circadian oscillator.Methods: We downloaded RNAseq count data from the Genotype-Tissue Expression (GTEx) project. Treating mechanical ventilation as a marker for intensive care, we stratified samples into acute death (AD) and intensive care (IC) groups based on the documented Hardy Death Scale. We restricted our analysis to the 25 tissues with >50 samples in each group. Using the edgeR package and controlling for collection center, gender, and age, we identified transcripts differentially expressed between the AD and IC groups. Overrepresentation and enrichment methods were used to identify gene sets modulated by intensive care across tissues. For each tissue, we then calculated the delta clock correlation distance (ΔCCD), a comparative measure of the functional organization of the core circadian oscillator, in the both the AD and IC groups. The statistical significance of the ΔCCD was assessed by permutation, modifying a pre-existing R package to control for confounding variables.Results: Intensive care, as marked by ventilation, significantly modulated the expression of thousands of genes. Transcripts that were modulated in ≥75% of tissues were enriched for genes involved in mitochondrial energetics, cellular stress, metabolism, and notably circadian regulation. Transcripts that were more markedly affected, in ≥10 tissues, were enriched for inflammation, complement and immune pathways. Oscillator organization, as assessed by ΔCCD, was significantly reduced in the intensive care group in 11/25 tissues.Conclusion: Our findings support the hypothesis that patients in intensive care have impaired molecular circadian rhythms. Tissues involved in metabolism and energetics demonstrated the most marked changes in oscillator organization. In adipose tissue, there was a significant overlap between transcripts previously established to be modulated by sleep deprivation and fasting with those modulated by critical care. This work suggests that intensive care protocols that restore sleep/wake and nutritional rhythms may be of benefit.

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Section: Introductionmentioning

confidence: 99%

Multi-tissue transcriptional changes and core circadian clock disruption following intensive care

2022

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The Role of the Body Clock in Asthma and COPD: Implication for Treatment

Krakowiak

Durrington

2018

Pulm Ther

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Asthma exhibits a marked time of day variation in symptoms, airway physiology, and airway inflammation. This is also seen in chronic obstructive pulmonary disease (COPD), but to a lesser extent. Our understanding of how physiological daily rhythms are regulated by the circadian clock is increasing, and there is growing evidence that the molecular clock is important in the pathogenesis of these two airway diseases. If time of day is important, then it follows that treatment of asthma and COPD should also be tailored to the most efficacious time of the day, a concept known as 'chronotherapy'. There have been a number of studies to determine the optimal time of day at which to take medications for asthma and COPD. Some of these agents are already used 'chronotherapeutically' in practice (often at night-time). However, several studies investigating systemic and inhaled corticosteroids have consistently shown that the best time of day to take these medications for treating asthma is in the afternoon or early evening and not in the morning, when these medications are often prescribed. Future, large, randomized, placebo-controlled studies of systemic and inhaled corticosteroids in asthma and COPD are needed to inform clinical practice.

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Disturbed circadian rhythm in ICU patients as indicated by melatonin levels: a prospective pilot study

Cited by 2 publications

References 3 publications

Multi-tissue transcriptional changes and core circadian clock disruption following intensive care

Multi-tissue transcriptional changes and core circadian clock disruption following intensive care

The Role of the Body Clock in Asthma and COPD: Implication for Treatment

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