Circadian disruption is pervasive and can occur at multiple organizational levels, contributing to poor health outcomes at individual and population levels. Evidence points to a bidirectional relationship, in that circadian disruption increases disease severity and many diseases can disrupt circadian rhythms. Importantly, circadian disruption can increase the risk for the expression and development of neurologic, psychiatric, cardiometabolic, and immune disorders. Thus, harnessing the rich findings from preclinical and translational research in circadian biology to enhance health via circadian-based approaches represents a unique opportunity for personalized/precision medicine and overall societal well-being. In this Review, we discuss the implications of circadian disruption for human health using a bench-to-bedside approach. Evidence from preclinical and translational science is applied to a clinical and population-based approach. Given the broad implications of circadian regulation for human health, this Review focuses its discussion on selected examples in neurologic, psychiatric, metabolic, cardiovascular, allergic, and immunologic disorders that highlight the interrelatedness between circadian disruption and human disease and the potential of circadian-based interventions, such as bright light therapy and exogenous melatonin, as well as chronotherapy to improve and/or modify disease outcomes.

Circadian disruption and human health.

Introduction Shift work is associated with lung disease and infections. We therefore investigated the impact of shift work on significant COVID-19 illness. Methods 501 000 UK Biobank participants were linked to secondary care SARS-CoV-2 PCR results from Public Health England. Healthcare worker occupational testing and those without an occupational history were excluded from analysis. Results Multivariate logistic regression (age, sex, ethnicity and deprivation index) revealed that irregular shift work (OR 2.42, 95% CI 1.92 to 3.05), permanent shift work (OR 2.5, 95% CI 1.95 to 3.19), day shift work (OR 2.01, 95% CI 1.55 to 2.6), irregular night shift work (OR 3.04, 95% CI 2.37 to 3.9) and permanent night shift work (OR 2.49, 95% CI 1.67 to 3.7) were all associated with positive COVID-19 tests compared with participants that did not perform shift work. This relationship persisted after adding sleep duration, chronotype, premorbid disease, body mass index, alcohol and smoking to the model. The effects of workplace were controlled for in three ways: (1) by adding in work factors (proximity to a colleague combined with estimated disease exposure) to the multivariate model or (2) comparing participants within each job sector (non-essential, essential and healthcare) and (3) comparing shift work and non-shift working colleagues. In all cases, shift work was significantly associated with COVID-19. In 2017, 120 307 UK Biobank participants had their occupational history reprofiled. Using this updated occupational data shift work remained associated with COVID-19 (OR 4.48 (95% CI 1.8 to 11.18). Conclusions Shift work is associated with a higher likelihood of in-hospital COVID-19 positivity. This risk could potentially be mitigated via additional workplace precautions or vaccination.

https://thorax.bmj.com/content/thoraxjnl/76/6/601.full.pdf

Shift work is associated with positive COVID-19 status in hospitalised patients.

Introduction Shift work is associated with both mental, and physical ill health, including lung disease and infections. However, the impact of shift work on significant COVID-19 illness has not be assessed. We therefore investigated whether shift work is associated with COVID-19. Methods 501,000 UK biobank participants were linked to secondary care SARS-CoV-2 PCR results from public health England. Healthcare workers and those without an occupational history were excluded from analysis. Results Multivariate logistic regression taking into account age, sex, ethnicity and deprivation index revealed that irregular shift work (OR 2.42 95%CI 1.92-3.05), permanent shift work (OR 2.5, 95%CI 1.95-3.19), day shift work (OR 2.01, 95%CI 1.55-2.6), irregular night shift work (OR 3.04, 95%CI 2.37-3.9) and permanent night shift work (OR 2.49, 95%CI 1.67-3.7) were all associated with positive COVID-19 tests compared to participants that did not perform shift work. This relationship persisted after adding sleep duration, chronotype, pre-morbid disease, BMI, alcohol and smoking. Work factors (proximity to a colleague combined with estimated disease exposure) were positively correlated with COVID-19 incidence (r2=0.248, p=0.02). If this was added to the model shift work frequency remained significantly associated with COVID-19. To control for non-measured occupational factors the incidence of COVID-19 in shift workers was compared to colleagues in the same job who did not do shift work. Shift workers had a higher incidence of COVID-19 (p Conclusions Shift work is associated with a higher likelihood of in-hospital COVID-19 positivity. This risk could potentially be mitigated via additional workplace precautions or vaccination.

/pdf/shift-work-is-associated-with-positive-covid-19-status-in-4e8eot25th.pdf

Shift work is associated with positive COVID-19 status in hospitalised patients

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.

/pdf/the-endogenous-circadian-system-worsens-asthma-at-night-51nyfhjsdn.pdf

The endogenous circadian system worsens asthma at night independent of sleep and other daily behavioral or environmental cycles.

Asthma and obstructive sleep apnoea in adults and children – an up-to-date review

Introduction Shift work causes misalignment between internal circadian time and the external light/dark cycle and is associated with metabolic disorders and cancer. Approximately 20% of the working population in industrialised countries work permanent or rotating night shifts, exposing this large population to the risk of circadian misalignment-driven disease. Analysis of the impact of shift work on chronic inflammatory diseases is lacking. We investigated the association between shift work and asthma. Methods We describe the cross-sectional relationship between shift work and prevalent asthma in >280000 UK Biobank participants, making adjustments for major confounding factors (smoking history, ethnicity, socioeconomic status, physical activity, body mass index). We also investigated chronotype. Results Compared with day workers, ‘permanent’ night shift workers had a higher likelihood of moderate-severe asthma (OR 1.36 (95% CI 1.03 to 1.8)) and all asthma (OR 1.23 (95% CI 1.03 to 1.46)). Individuals doing any type of shift work had higher adjusted odds of wheeze/whistling in the chest. Shift workers who never or rarely worked on nights and people working permanent nights had a higher adjusted likelihood of having reduced lung function (FEV1 Conclusions The public health implications of these findings are far-reaching due to the high prevalence and co-occurrence of both asthma and shift work. Future longitudinal follow-up studies are needed to determine if modifying shift work schedules to take into account chronotype might present a public health measure to reduce the risk of developing inflammatory diseases such as asthma.

https://thorax.bmj.com/content/thoraxjnl/76/1/53.full.pdf

James Turner

Papers

Night shift work is associated with an increased risk of asthma