Physiological Responses in Young and Older Adults During a Prolonged Simulated Heatwave
Condition: Aging; Heat Stress; Physiological Stress
MeSH terms: Heat Stress Disorders
Study type: Interventional

Summary: 
      Climate change not only affects the planet's natural resources, but also severely impacts
      human health. 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 efficiently regulate body temperature. However, information regarding the impact
      of age on body temperature regulation during prolonged exposure to extreme heat is lacking,
      as is research on the effectiveness of interventions aimed at reducing heat strain in such
      situations. This project will address these important knowledge gaps by exposing healthy
      young and older adults to a prolonged (9 hour) heat exposure, with conditions representative
      of heatwaves in temperate continental climates. An additional cohort of older adults will
      complete the same heatwave simulation but will be briefly (2 hours) exposed to cooler
      conditions (22-23°C) mid-way through the session (akin to visiting a cooling centre or cooled
      location). The investigators will evaluate age-related differences in the capacity to
      dissipate heat via direct air calorimetry (a unique device that permits the precise
      measurement of the heat dissipated by the human body) and their effect on the regulation of
      body temperature. The investigators anticipate that older adults will exhibit progressive
      increases in the heat stored in the body throughout the simulated heatwave, resulting in
      progressive increases in body core temperature. Further, older adults exposed to brief-mid
      day cooling will rapidly gain heat upon re-exposure to high ambient temperatures. As a
      result, by the end of exposure body temperatures will be similar to the group not removed
      from the heat.
    

Detailed description: 
      OBJECTIVES Intervention 1: Evaluate the effect of age on whole-body heat storage, body core
      temperature, and the development of cardiovascular strain and acute inflammation during
      day-long (9 hours) exposure to simulated heatwave conditions.

      Intervention 2: Determine whether short-duration exposure (2 hours) to an air-conditioned
      environment following extreme heat exposure results in lasting reductions in physiological
      strain in older adults upon return to the heat.

      Hypotheses Intervention 1: Older adults will experience greater heat storage throughout the
      9-hour simulated heatwave compared to the younger participants. Consequently, body core
      temperature will be greater in the older adults and between-group differences will be
      exacerbated as exposure progresses. We will also explore the secondary hypothesis that
      differences in body temperature will be paralleled by greater alterations in cardiovascular
      variables and acute circulatory and intracellular inflammation in the older adults.

      Intervention 2: Body heat storage will be exacerbated in the older adults exposed to the
      cooling centre intervention upon return to the heat (hours 5-6) compared to the older adults
      from Intervention 1 who remained in the heat. Consequently, body core temperature will be
      comparable (statistically equivalent) between groups by the end of exposure.

      Methods Participants A total of 20 young (age: 18-31 years) and 40 older (age: 64-80 years)
      adults will be recruited for the proposed project, with an approximately even distribution of
      men and women in each intervention arm. Young (n = 20) and older (n = 20) adults will
      complete Intervention 1 and a separate cohort of older adults (n = 20) will complete
      Intervention 2. Participants will be homogenous for anthropomorphic characteristics as well
      as habitual physical activity levels as verified via standardized questionnaires.

      Experimental Design Pre-trial instructions All participants will be asked to avoid strenuous
      physical 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
      (urine specific gravity <1.025). For all sessions, participants will wear athletic shorts
      (and a sport top for women).

      Preliminary screening All participants will complete one preliminary evaluation a minimum of
      7 days before the first experimental session. During this session they will be familiarized
      with all 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. 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.

      Experimental Protocol (Intervention 1) Each session will commence at 07:00-09:00. Upon
      arrival to the laboratory, the participant will provide a urine sample for the assessment of
      urine specific gravity, after which a measurement of nude body mass will be obtained.
      Participants will then insert a temperature probe for the continuous measurement of rectal
      temperature. Thereafter, participants will be instrumented for the measurement of skin
      temperature and 5-lead echocardiogram. Baseline cardiovascular parameters will be evaluated
      via a brief (~45 min) cardiovascular test battery, performed as follows. Brachial arterial
      systolic and diastolic pressures reconstructed from arterial pressure waveforms measured at
      the right middle finger (volume clamp technique) and 5-lead echocardiogram recordings will be
      collected for 10-min while the participant rests quietly (spontaneous breathing). Immediately
      thereafter, arterial systolic and diastolic pressures will be measured in triplicate via
      manual auscultation (~30 sec between measures), after which forearm and calf blood flows on
      the right side of the body will be measured via automated venous occlusion plethysmography.
      Throughout the test battery, the participant will be seated with both feet on the floor,
      except for during the measurements of limb blood flow, where the instrumented limbs will be
      elevated to facilitate venous drainage. Finally, a venous blood sample and body mass
      measurement will be obtained.

      Participants will then be transferred to the whole-body direct calorimeter chamber, regulated
      to 40°C and ~10-15% humidity. These conditions were chosen to simulate peak temperatures
      experienced during heatwaves and are similar to peak conditions in recent heatwaves in North
      America in 2018 (Ottawa, Ontario; 34°C and 58%, heat index: 41°C) and Europe in 2003 (Paris,
      France; 38°C and 25%, heat index: 38°C). The participant will rest quietly for 3-hours (hours
      1-3) within the calorimeter chamber while whole-body heat production and exchange are
      measured continuously. At the 3-hour mark, the participant will exit the calorimeter and the
      brief cardiovascular test battery will be performed again followed by a measurement of body
      mass. Hours 4-6 will be spent resting in the heat in the thermal chamber adjacent to the
      calorimeter. During this time, participants will be allowed to consume a light, self-provided
      lunch with low water content. Tap water will be provided ad libitum via a self-service
      insulated water cooler located in the thermal chamber. Another cardiovascular battery will
      then be performed followed by a measurement of body mass. The participant will then re-enter
      the calorimeter where the final 3 hours will be spent (hours 6-9). At the end of this period,
      the participants will undergo a fourth and final cardiovascular test battery and a final
      venous blood sample and body mass measurement will be procured.

      Statistical analysis and sample size calculations Primary and secondary variables will be
      evaluated using linear mixed-effects models. Time will be modelled as a repeated
      within-subject fixed effect, and age-group will be modelled as a between-subject fixed
      effect. Pre-heat exposure values of the outcome variable, participant sex, and self-reported
      weekly physical activity (min/week, as assessed via the GAQ) will be included as covariates.
      Participant identification will be modeled as a random effect in all analyses. Akaike's
      information criterion will be used to determine random effect and variance/covariance
      structures.

      Post hoc multiple comparisons will be made on model estimated marginal means. Given the small
      number of comparisons for each variable, multiplicity corrections will not be employed.
      Homoscedasticity will be evaluated for all models by visual assessment of residual plots.
      Approximate normal distribution of residuals will be assessed via visual inspection of
      histograms and Q-Q plots. Data will be log-transformed in the event that the distribution of
      residuals meaningfully deviates from normality. For all analyses, alpha will be set at 0.050.
      Descriptive statistics will be presented as means and standard deviations. Comparisons
      between groups and/or time-points will be presented as means and 95% confidence intervals
      [lower limit, upper limit].

      An a priori power analysis determined that a total sample size of 19 young and 19 older
      adults was required to detect a difference in the rate of whole-body heat storage between
      groups at the end of each calorimeter session (i.e., hours 3 and 9) with 80% statistical
      power. In lieu of clinically meaningful data (i.e., what would be considered a clinically
      meaningful change in whole-body heat storage), the standardized effect size (Cohen's d=1.06)
      was calculated based on the difference in the rate of whole-body heat storage between young
      and older adults over the final 30-min of a 3-hour heat exposure protocol (young: -2 [26]
      kJ/hour, older: 43 [54] kJ/hour) in our previous work.

      Experimental Protocol (Intervention 2) Experimental design The protocol for Intervention 2 is
      identical to that of Intervention 1 except that after the first calorimeter session and
      subsequent cardiovascular battery, participants will exit the thermal chamber and spend ~2
      hours (hours 5-6) resting in an air-conditioned room (~23°C, ~50% relative humidity). Similar
      to Intervention 1, participants will be allowed to eat a small self-provided lunch during
      this time and consume water (tap) ad libitum. The third cardiovascular battery will also be
      performed in the cooled environment. As in Intervention 1, participants will then re-enter
      the calorimeter for the final 3 hours, where they will rest in the heat for the remainder of
      the experimental session.

      Statistical analysis and sample size calculations Statistical analysis for Intervention 2
      will be performed to assess whether mid-day exposure to a cooled room results in greater body
      heat storage following exposure such that physiological responses are similar to those of the
      non-cooled group by the end of the 9-hour heatwave simulation. Cumulative whole-body heat
      storage will be evaluated using a linear mixed-effects model with experimental group modelled
      as a between-subject fixed effect. Cumulative heat storage over the first three hours of the
      9-hour exposure will be included as a covariate to account for the influence of any inter- or
      intra-individual factors (e.g., sex, physical activity levels), measured or unmeasured,
      impacting whole-body heat exchange and storage. Comparisons of heat storage between groups
      will be made using model estimated marginal means.

      Body core temperature, as estimated by rectal temperature (primary outcome), will be analyzed
      with a linear mixed effects model with experimental group (two levels: cooling and
      no-cooling) modelled as a between-subject fixed effect and time as a repeated within-subject
      fixed effect (0-, 1-, 2-, and 3-hours post-cooling intervention). Like the model for heat
      storage, rectal temperature at the end of the first calorimetry session (i.e., hour 3 of the
      9-hour exposure) will be included as a covariate to account for the influence of any measured
      or unmeasured inter- or intra-individual factors impacting the body temperature responses to
      resting heat exposure.

      The effect of cooling on rectal temperature will then be assessed via two one-sided tests
      performed on the mixed-effects model derived estimated marginal means at each timepoint.
      Equivalence bounds will be set to ±0.3°C, which corresponds to the typical day-to-day
      variation of core temperature and has been suggested to reflect a meaningful/detectable
      change in body temperatures in a recent study assessing the influence of cooling strategies
      on physiological strain in young adults. Secondary variables will be similarly evaluated. The
      level of significance will be set at P < 0.050. Descriptive statistics will be presented as
      mean (standard deviation) and comparisons between groups will be presented as mean ± 95%
      confidence interval.

      An a priori power analysis determined that a total sample size of 18 older adults in each
      group (36 participants total) is required to confirm whether between-group differences in
      rectal temperature are equivalent within upper and lower bounds of +0.3°C and -0.3°C,
      respectively, with 80% power. This corresponds to an effect size (Cohen's d) of 1.0, based on
      the pooled-standard deviation of 0.3°C, determined from published data from our laboratory
      demonstrating 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.
    

Intervention name(s): Simulated heatwave exposure; Simulated heatwave exposure with mid-day cooling
Intervention type(s): Other; Other
Intervention description(s): Young and older adults (no cooling) are exposed to a 9-hour simulated exposure.; Older adults (cooling) are exposed to a 9-hour simulated exposure with mid-day ambient cooling.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Heatwave; Heat-vulnerability; Cooling center; Heat strain; Cardiovascular responses