Establishing Evidence-based Indoor Temperature Thresholds to Protect Health
Condition: Aging; Heat Stress; Physiological Stress
MeSH terms: Heat Stress Disorders
Study type: Interventional

Summary: 
      An individual's ability to adequately cope with short- or long-term increases in ambient
      temperature is critical for maintaining health and wellbeing. Prolonged increases in
      temperature (heatwaves) pose a serious health risk for older adults, who have a reduced
      capacity to regulate body temperature. Currently, however, there is a lack of information
      regarding how different environmental conditions experienced during heatwaves impact body
      temperature regulation and physiological function. This is particularly important in the
      context of ambient conditions in the home, where older adults spend the majority of their
      time. This project will address this important issue by exposing healthy older adults to
      prolonged (8-hour) simulated heatwaves comprising a range of environmental conditions
      representative of an actively cooled domicile through to a worst-case scenario (i.e., no
      capacity for home cooling). The investigators will directly measure their ability to regulate
      their body temperature and the associated impact on the autonomic control of the heart. The
      investigators anticipate that physiological strain will be mild during prolonged exposure to
      conditions below the currently recommended thresholds set by Toronto Public Health (26°C).
      However, at higher indoor temperatures, impairments in body temperature and cardiovascular
      regulation will be seen.
    

Detailed description: 
      OBJECTIVES

      The objective of this project is to evaluate the effect of a range of environments
      experienced during heatwaves on body temperature and autonomic cardiovascular function in
      older adults. This will be accomplished by comparing thermal and cardiovascular responses in
      a group of older adults resting for 8-hours in a range of conditions representative of those
      experienced indoors during heatwaves. To assess how the strain experienced in these
      conditions affects haemodynamic regulation in turn, this study will also include validated
      tests of cardiovascular autonomic function.

      Hypotheses

      Indices of thermal and cardiovascular strain will not be appreciably modified in older adults
      resting in simulated indoor environments below the currently recommended thresholds set by
      Toronto Public Health (22°C and 26°C). However, at higher indoor temperatures (31°C and 36°C)
      thermal and cardiovascular responses will be elevated. The increased physiological strain in
      these conditions will be reflected in attenuated responses to validated cardiovascular
      autonomic functional tests.

      METHODS

      Participants A total of 16 older (age: 65-80 years) adults will be recruited for the proposed
      project with an approximately even distribution of men and women. Each participant will
      complete each of the 4 experimental arms of the study. Recruited participants will be
      homogeneous for anthropomorphic characteristics and as well as habitual physical activity
      levels as verified via standardized questionnaires (determined during a preliminary session).
      Written and informed consent will be obtained from all volunteers prior to participation.

      Study Design

      Pre-trial instructions

      All participants will be asked to avoid strenuous activity and alcohol for 24 hours prior to
      all preliminary and experimental sessions and to eat a light meal 2 hours before the start of
      each session. Participants will also be asked to consume a minimum of 500 ml of water the
      night before and morning of each session to ensure adequate hydration. Adequate hydration
      will be verified upon arrival to the laboratory via urine specific gravity (urine specific
      gravity <1.025). Participants will wear an athletic top and shorts for all sessions.

      Preliminary screening

      All participants will complete one preliminary evaluation a minimum of 48 hours before the
      first experimental session. During this session they will be familiarized with all
      experimental procedures and measurement techniques and will complete the Get Active
      Questionnaire (GAQ) and the American Heart Association Pre-participation screening
      Questionnaire to assess their eligibility to participate. The GAQ will also be used to assess
      habitual activity levels along with the Kohl Physical Activity Questionnaire. Participants
      will also provide verbal and written informed consent at this time. Thereafter, participant
      physical characteristics will be evaluated. Body height and mass will be determined via a
      physician stadiometer and a high-performance weighing terminal, respectively, and from these
      measurements body surface area will be calculated. Body density will be estimated via
      hydrostatic weighing and used to calculate body fat percentage.

      Experimental Protocol Each experimental session will commence at approximately 08:00. Upon
      arrival to the laboratory the participant will provide a urine sample for measurement of
      urine specific gravity and insert a rectal temperature probe. Thereafter, participants will
      be instrumented for the measurement of skin temperature. A measurement of body mass (nude)
      will also be taken at this time. Participants will then be transferred to a thermal chamber
      regulated to 22°C and 45%. Following 10-min of supine rest, participants will perform a
      specialized cardiovascular test battery (see below). They will then rest in the seated
      position in a room immediately adjacent to the thermal (~22°C) chamber for ~30 min while
      baseline body temperatures and cardiovascular measures are recorded. A venous blood sample
      will be obtained at this time.

      While baseline measurements are being taken, the thermal chamber will be heated to the
      conditions for that day's session. Each participant will complete four separate sessions
      consisting of resting exposure to: i) 36°C, based on maximal measured indoor temperatures
      (i.e., 35°C) and similar to outdoor conditions experienced during recent heatwaves in North
      America (HOT); ii) 31°C, similar average daytime temperature during the 2010 heatwave in
      Ontario and Quebec as well as the World Health Organization recommended indoor temperature
      limit during heatwaves (WARM); iii) 26°C corresponding to recommended upper limits for indoor
      environments as set by Toronto Public Health (TEMPERATE) and iv) 22°C, to simulate an
      air-conditioned environment (COOL). In all sessions, relative humidity will be set to 45%.

      Following baseline, the participant will enter the thermal chamber where they will rest for 8
      hours. They will spend the majority of this time in the seated (slightly reclined) position,
      except for at the 6th hour where they will again perform the cardiovascular test battery.
      Rectal and skin temperatures and heart rate will be measured continuously throughout
      exposure. Tap water will be provided ad libitum from a ~500 mL cup placed on a side-table
      positioned slightly behind the participant. Participants will also be allowed to eat a
      self-provided lunch between hours 1.5 and 3.5 of exposure. Every 60 min, arterial blood
      pressure and heart rate will be measured in triplicate after which participants will stand to
      provide a measurement of body mass in order to determine sweat losses. At this time.
      participants will be allowed to remain standing and briefly perform light stretching, if
      desired (max ~5 min).

      Autonomic control of heart rate and blood pressure will be assessed prior to and at the end
      of each session using a battery of cardiovascular tests, which, in Study B consists of: i)
      analysis of heart rate variability and spontaneous baroreflex sensitivity during supine rest,
      ii) Ewing's battery (modified) for assessment of cardiovascular autonomic function, and iii)
      analysis of integrated baroreflex sensitivity during cyclical perturbations in arterial
      pressure evoked by stand-squat maneuvers. Prior to the battery, participants will be
      instrumented with an integrated 3-lead ECG non-invasive blood pressure monitor for the
      integrated measurement of beat-to-beat heart rate and arterial blood pressure, estimated from
      the arterial pressure waveform measured at the left middle finger. The same researcher will
      administer the battery for all sessions. Finally, note that the first two sections of the
      battery described below will be performed twice in succession prior to the stand-squat
      procedures.

      Following 8-min of supine rest, heart rate variability (HRV) and baroreflex sensitivity (BRS)
      will be evaluated during 8-min of supine rest. Participants will be instructed to breathe
      (diaphragmatic) in time with a metronome set to 30 beats/min, to remove the influence of
      respiratory sinus rhythm on cyclical fluctuations in heart rate and blood pressure.
      Thereafter, the metronome will be stopped and 1-min of recovery will be given prior to the
      start of the Ewing's battery.

      The modified Ewing's battery to be employed consists of three tests designed to assess
      autonomic control of heart rate and blood pressure. First, participants perform 1 min of deep
      diaphragmatic breathing at a rate of 6 breaths/min. Breathing will be performed to vital
      capacity - that is, through a maximal inspiration and expiration. 5-min of recovery will be
      given before the next test. The next test is the Valsalva maneuver. While still in the supine
      position, participants will exhale against a closed glottis into a narrow vinyl tube
      connected to an electronic pressure transducer that will be used to provide constant feedback
      to the participant on the generated expiratory pressure. The participant will be instructed
      to maintain a constant pressure of 40 mmHg for 15 s. Throughout expiratory straining, air
      will be vented via a small bleed to prevent generation pressure via the mouth. Upon release,
      heart rate and blood pressure will be monitored for 1 min. The final test is the
      lying-to-standing test. Following 1-min of rest in the supine position, the participant is
      instructed to quickly assume a standing position directly beside the bed. The participant
      then stands quietly for 3 min while heart rate and blood pressure are monitored.

      Following the second Ewing's battery, the participant will rest in the seated position on a
      rigid chair for 10 mins. The participant will then be asked to stand for 90-seconds while the
      positioning of the sling and finger-pressure cuff is adjusted (if needed) to ensure the left
      hand is maintained at heart-level. After this, 5-min of squat-stands will be performed at a
      rate of 6 cycles/min. Each cycle will consist of a squat, held for 5 seconds, followed by
      standing for 5 sec. For these maneuvers, participants will be instructed to maintain a
      consistent depth for each squat, breath normally to avoid expiratory straining and limit
      excessive forward flexion at the hip.

      After the cardiovascular battery, participants will remain seated in the chamber for the
      remainder of the 8-hour exposure (~45 min). Following measurements of arterial blood
      pressure, a final venous blood sample will be obtained followed by a measurement of body
      mass. The participant will be provided with water and/or a commercially available sports
      drink before leaving laboratory.

      Data analysis

      Continuous variables related to thermal strain and cardiovascular strain will be converted to
      15-min averages for baseline and at each hour of exposure. Likewise, seated arterial
      pressures (3 measurement average) will be presented at these time points. Rate pressure
      product will be calculated as the product of heart rate and systolic blood pressure. The
      change in body mass from baseline values will also be determined at each hour of exposure to
      quantify the rate of fluid loss, corrected for fluid consumed and urination. The change in
      plasma volume and serum osmolality from baseline to end exposure will also be calculated from
      the venous blood samples obtained at the start and end of each session. HRV and resting
      spontaneous cardiac BRS will be determined from data collected during the 8-min controlled
      breathing period. Similarly, integrated BRS will be derived from collected blood pressure and
      ECG waveforms collected during the stand-squat maneuvers.

      For the clinically validated tests in the Ewing battery, analysis will be performed by a
      trained researcher blinded to the participant and session code (i.e., environmental
      conditions). Deep breathing will be analysed as the difference in heart rate between the
      average of the three lowest and three highest values recorded during inspiration and
      expiration, respectively (E/I HRDiff). For the Valsalva maneuver, the so-called Valsalva
      ratio (VALratio) is calculated as the longest R-R interval during recovery divided by the
      shortest R-R interval during straining. Finally, the lying to standing test is analysed by
      determination of the 30:15 ratio, which represents the longest RR interval measured between
      the 25-35th heart beat upon standing divided by the shortest RR interval between the 10-20th
      beat after standing. Additionally, the systolic response to standing (SRstand) is also taken
      as the 1-min average of systolic blood pressure after the second min of standing divided by
      systolic blood pressure during the pre-stand supine resting period (i.e., the reduction in
      systolic pressure upon assuming a standing position). Values for each test will be taken as
      the average of each of the two recorded values.

      Statistical analysis and sample size calculation

      Statistical analysis will compare end-exposure data relating to thermal and cardiovascular
      strain as well as autonomic function (while correcting for between-session baseline
      variability). Body temperature and cardiovascular responses at the end of exposure (i.e.,
      hour 8) as well as the autonomic functional tests of the cardiovascular battery will be
      evaluated using an analysis of covariance (ANCOVA) with the repeated factor of environmental
      condition and baseline values modeled as a continuous covariate. Variables related to fluid
      loss (e.g., change in body mass, plasma volume and serum osmolality) will be analysed via a
      one-way ANOVA with the factor of condition (4 levels). For all statistical models,
      homogeneity of variances will be assessed using Levene's test. Normal distribution of
      residuals will be assessed with Sharpiro-Wilks test and visual inspection of histograms and
      Q-Q plots and data will be log-transformed in the event that distribution of residuals
      deviates from normality. Pre-planned post hoc comparisons will be employed to identify
      differences between adjacent conditions (e.g., COOL vs TEMP, TEMP vs. WARM, WARM vs. HOT) in
      order to limit a large family of comparisons. For all analyses, alpha will be set at P <
      0.050. Descriptive statistics will be presented as mean (standard deviation). Comparisons
      between groups or time-points (where appropriate) will be presented as means ± 95% confidence
      interval.

      An a priori power analysis determined that a total sample size of 16 older adults is required
      to detect a difference in rectal temperature between groups with 80% statistical power, after
      adjusting for multiple comparisons. The effect size (Cohen's d=1.0) was determined based on
      practically meaningful difference of 0.3°C between conditions, assuming a standard deviation
      of 0.3. The standard deviation was based on previously published studies from our laboratory,
      which demonstrated a 0.2°C (SD 0.3) difference in core temperature between young and older
      adults and a 0.0°C (SD 0.3) difference in core temperature between older adults with and
      without type 2 diabetes following 3 hours of rest in a hot environment (40°C, 30% relative
      humidity).
    

Intervention name(s): Simulated heatwave exposure
Intervention type(s): Other
Intervention description(s): Older adults are exposed to a 8-hour simulated exposure
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Heatwave,; heat-vulnerability; Indoor environments; Cardiovascular strain; thermoregulation; heat strain