Relevance of a Mobile Internet Platform for Capturing Inter- and Intrasubject Variabilities in Circadian Coordination During Daily Routine: Pilot Study.

Sandra Komarzynski,Qi Huang,Nicolas Beaumatin,Mohamed Bouchahda,Jacques Beau,Alexandre Arbaud,Bärbel Finkenstädt,Pasquale F Innominato,Francis Lévi,Gabrièle Breda,Ayhan Ulusakarya,Monique Maurice

doi:10.2196/jmir.9779

Abstract

BackgroundExperimental 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.ObjectiveThe objective was to evaluate the circadian clocks’ coordination in healthy subjects and patients through simultaneous measurements of rest-activity and body temperature rhythms.MethodsNoninvasive real-time measurements of rest-activity and chest temperature rhythms were recorded during the subject’s daily life, using a dedicated new mobile electronic 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 General Packet Radio Service every 24 hours. 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.ResultsAll 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 hours for 51 out of 67 subjects (76%), and around 12 hours for 13 others (19%). Statistically significant sex- and age-related differences in circadian coordination were identified in the noncancerous 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 noncancerous people and 33% (4/12) of the cancer patients, thus supporting important intersubject differences in circadian coordination. Sex, age, and cancer significantly impacted the circadian coordination of both rhythms, based on their phase relationships.ConclusionsComplementing rest-activity with chest temperature circadian e-monitoring revealed striking intersubject 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.

Highlights

BackgroundCircadian rhythms regulate mammalian physiology, as well as cell metabolism, proliferation, and survival over the 24 hours
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
As response variable Y, we considered a selection of estimated circadian parameters that summarized the behavior of the biomarkers for each subject, including (1) the amplitude of the main period of temperature, which was obtained from spectral estimation; (2) the amplitude of activity, during prolonged activity spans, as approximated by the interquartile range (IQR) or amplitude of 50% central values of observed values; (3) the spectral gravity center of temperature; and (4) the spectral gravity center of rest-activity

Summary

Introduction

Circadian (about-24-hour) rhythms regulate mammalian physiology, as well as cell metabolism, proliferation, and survival over the 24 hours These rhythms play an important role in disease processes and treatment effects, which has been largely overlooked in medicine [1,2,3]. Treatment effects could differ according to circadian timing or chronomodulated scheduling of medications in a consistent fashion across individual subjects with a similar circadian entrainment [1,10,11,12] Such standardized approaches to chronotherapy proved valid in experimental rodents of same sex, strain, and age, which were synchronized with the same alternation of 12-hours of light and darkness, especially for anticancer drugs [1,13]. We hypothesized that concurrent measurements of body temperature and rest-activity rhythms would assess circadian clocks coordination in individual patients, enabling the integration of biological rhythms into precision medicine

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