Circadian Disruption in Night Shift Work and Its Association with Chronic Pulmonary Diseases

Abstract

Globalization and the expansion of essential services over continuous 24 h cycles have necessitated the adaptation of the human workforce to shift-based schedules. Night shift work (NSW) causes a state of desynchrony between the internal circadian machinery and external environmental cues, which can impact inflammatory and metabolic pathways. The discovery of clock genes in the lung has shed light on potential mechanisms of circadian misalignment in chronic pulmonary disease. Here, the current knowledge of circadian clock disruption caused by NSW and its impact on lung inflammation and associated pathophysiology in chronic lung diseases, such as asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and COVID-19, is reviewed. Furthermore, the limitations of the current understanding of circadian disruption and potential future chronotherapeutic advances are discussed.

Keywords: asthma; chronic obstructive pulmonary disease; circadian disruption; clock genes; night shift work; pulmonary fibrosis.

Figure 1:. Circadian clock machinery in the lung

The schematic representation of the transcriptional-translational feedback loop (TTFL) system drives the periodic oscillation of circadian clock genes and proteins at the cellular level in the lung. The TTFL system is divided into three-loop systems, which interact with each other through transcriptomic products. Details of this regulatory system can be found in the section ‘Understanding the mammalian biological clock machinery‘. This figure was partly created using Servier Medical Art (smart.servier.com). Abbreviations: BMAL1- Brain and muscle ARNT-Like 1, CLOCK- Circadian locomotor output cycles kaput, CRY-Cryptochrome, PER- Period, DBP- D-box binding protein, NFIL3- Nuclear Factor Interleukin 3 regulated, ROR- Retinoic acid-related orphan receptor.

Figure 2:. Circadian clock disruption due to night shift work in pulmonary disease

The schematic representation on the effect of night shift work-induced circadian clock disruption associated with lung inflammation and chronic lung diseases. The impact of circadian gene transcription and/or translation can also extend to other metabolic diseases in night shift workers. This figure was partly created using Servier Medical Art (smart.servier.com). Abbreviations: Per-Period, Cry-cryptochrome, Clock- circadian locomotor output cycles kaput, Nr1d1/2- Nuclear Receptor Subfamily 1 Group D Member 1/2, ROR- Retinoic acid-related orphan receptor, Dec1- deleted in esophageal cancer 1, Csnk1e- casein kinase 1 epsilon, KCNV2- potassium voltage-gated channel modifier subfamily V member 2, CAMK2D- calcium/calmodulin-dependent protein kinase II delta, Stat3- signal transducer and activator of transcription 3, PRDX2- peroxiredoxin 2, ABCA1- ATP binding cassette subfamily A member 1, SCL3A2- solute carrier family 3 member 2, GHRL- ghrelin and obestatin prepropeptide, ROS- Reactive oxygen species.