Relevance of a mobile internet platform for capturing inter- and intrasubject variabilities in circadian coordination during daily routine : pilot study

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Abstract

Background:

Experimental and epidemiologic studies have shown that circadian clocks disruption can play an important role in the development of cancer and metabolic diseases. The cellular clocks outside the brain are effectively coordinated by the body temperature rhythm. We hypothesized that concurrent measurements of body temperature and rest-activity rhythms would assess circadian clocks coordination in individual patients, thus enabling the integration of biological rhythms into precision medicine.

Objective

The objective was to evaluate the circadian clocks’ coordination in healthy subjects and patients through simultaneous measurements of rest-activity and body temperature rhythms.

Methods

Non-invasive real-time measurements of rest-activity and chest temperature rhythms were recorded during the subject’s daily life, using a dedicated new mobile e-health platform (PiCADo). It involved a chest sensor that jointly measured accelerations, 3D-orientation and skin surface temperature every 1-5 min, and relayed them out to a mobile gateway via Bluetooth-Low-Energy. The gateway tele-transmitted all stored data to a server via GPRS every 24 h. The technical capabilities of PiCADo were validated in 55 healthy subjects and 12 cancer patients, whose rhythms were e-monitored during their daily routine for 3-30 days. Spectral analyses enabled to compute rhythm parameters values, with their 90% confidence limits, and their dynamics in each subject.

Results

All the individuals displayed a dominant circadian rhythm in activity with maxima occurring from 12:09 to 20:25. This was not the case for the dominant temperature period, which clustered around 24 h for 51 out of 67 subjects (76%), and around 12 h for 13 others (19%). Statistically significant sex- and age- related differences in circadian coordination were identified in the non-cancerous subjects, based upon the range of variations in temperature rhythm amplitudes, maxima (acrophases), and phase relations with rest-activity. The circadian acrophase of chest temperature was located at night for the majority of people, but it occurred at daytime for 26% (14/55) of the non-cancerous people and 33% (4/12) of the cancer patients, hence supporting important inter-subject differences in circadian coordination. Sex, age and cancer significantly impacted on the circadian coordination of both rhythms, based on their phase relationships.

Conclusions

Complementing rest-activity with chest temperature circadian e-monitoring revealed striking inter-subject differences regarding human circadian clocks coordination and timing during daily routine. To further delineate the clinical importance of such finding, the PiCADo platform is currently applied for both the assessment of health effects resulting from atypical work schedules, and the identification of the key determinants of circadian disruption in cancer patients.

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