Interaction Effects of Temperature and Ozone
Condition: Exposure to Environmental Pollution, Non-occupational
Study type: Interventional

Summary: 
      Purpose: The purpose of this protocol is to understand how individuals respond to the air
      pollutant ozone at elevated temperatures. Ultimately, this will help us understand what the
      risks from poor air quality are during a heat wave.

      Participants: We will recruit up to 30 healthy adults, 18-55 years old, to participate in
      this study.

      Procedures (methods): Subjects will be exposed to clean air and to 0.3 ppm of ozone for 2
      hours with intermittent exercise in a controlled environment chamber. For each exposure the
      temperature in the chamber will be between 31-34oC (88-93 oF). Because the aim of the study
      is to mimic high exposure during a heat wave, we will perform exposures only on days when
      mean ambient temperatures was less than 24 oC in Chapel Hill on the previous day.

      Primary endpoints will include spirometry and Heart Rate Variability monitoring. Secondary
      endpoints will include analysis of blood clotting/coagulation factors, and analysis of
      soluble factors present in plasma.
    

Detailed description: 
      Over the past decades, air quality in the U.S. has improved significantly. Even so, millions
      of people in the U.S. still live in counties that do not meet air quality standards for one
      or more pollutants. Global climate change is widely accepted to be occurring and is thought
      to have a range of major and potentially adverse effects on the ecosystem. Additionally,
      changes in the climate can lead to higher concentrations of harmful air pollutants, and the
      presence of some air pollutants in the atmosphere can also accelerate climate change. Health
      effects are impacted by complex interactions between climate change and air quality. Research
      is needed to identify the public health consequences of these interactions. One aspect that
      has been understudied is how physiological responses to elevated temperature are impacted by
      the additional stressor of air pollution.

      Several epidemiological studies have shown a strong link between exposure to air pollution
      and adverse cardiopulmonary effects, such as respiratory tract infections, exacerbation of
      asthma, chronic bronchitis, ischemic heart disease, and stroke [1-3]. Ozone is a major
      component of photochemical smog. Controlled human exposure studies have been critical in
      demonstrating that it can cause decrements in lung function [4-10] and lung
      inflammation.[11-13] The inflammation includes increased neutrophils and soluble
      pro-inflammatory mediators in the lower airways [14, 15].

      The majority of these studies involved controlled exposures to relatively high (0.1 - 0.4ppm)
      concentrations for short periods of time (typically 2 hours). These short-term exposure
      studies are useful because a) they provide the strongest and most quantifiable
      exposure-response data and b) they allow the investigation of biological changes that in
      themselves are transient and inconsequential but can be extrapolated to predict health
      outcomes in susceptible populations or in long-term exposures. For example, healthy
      individuals exposed to 0.4ppm ozone exposure for 2hr [16] showed a13.5 % decrement in FEV1,
      often accompanied by only mild symptoms such as tracheobronchial irritation and cough.
      However, by 3hours after exposure, these symptoms had largely disappeared and only a 2.7%
      FEV1 decrement was detectable. By 24hrs, even at higher ozone concentrations the recovery
      phase has normally completed. The primary public health concern is in individuals with
      respiratory disease. If these same changes occurred in a person with reduced reserve, the
      ozone-induced changes would be superimposed on preexisting pulmonary impairment and may have
      significant health effects.

      Despite almost 30 years of research into the effects of ozone, there are very few studies of
      the interaction between ozone and temperature. Although ozone is normally elevated when the
      weather is dry and hot, most controlled chamber studies are performed at moderate
      temperatures (70-75 oF). Those studies that addressed higher temperatures were generally
      performed in the run-up to the Los Angeles Olympics in 1984 and centered on impairment of
      exercise performance. For example, Gibbons and Adams studied ten aerobically trained young
      adult females exercised continuously at 66% of maximum O2 uptake for 1 h while exposed orally
      to filtered air and 0.15 and 0.30 ppm ozone in both moderate (24 degrees oC) and hot (35
      degrees oC) ambient conditions and showed that subjects were more likely to cease exercising
      prematurely at hot temperatures.[17] Gong studied elite cyclists and showed similar
      results.[18] Folinsbee et al., studied the effects of a 2-h exposure to high level ozone (0.5
      ppm) in 14 nonsmoking males under four environmental conditions (64.4, 80.0, 85.2, and 92.0
      oF) and found that the greatest decrease in FVC occurred when ozone exposures were at the
      highest temperature.[19]

      Those cited studies have focused on respiratory outcomes. Yet it is becoming clear that ozone
      may have systemic and cardiac effects. Ozone reacts rapidly with respiratory tissues and is
      not absorbed or transported to extrapulmonary sites. However, recent studies have also shown
      associations between long-term ozone exposure and cardiovascular morbidity [20, 21]. In
      addition, short-term exposures to ozone may cause minor transient changes in high frequency
      heart rate variability (HRV) in healthy adults [22]. Experimental studies have shown that
      heat stress can have a similar modest effect on this component of HRV. [23] The effect of the
      combination has not been studied to date. Epidemiology studies assessing the
      ozone-temperature-cardiac relationship have generally been uninformative since high ozone
      days normally occur during hot weather. Traditional methods are not suitable to discriminate
      between the effects of ozone and temperature, let alone their interaction. Those that have
      studied the relationship have shown a negative association between temperature and
      ozone-mortality due to increased use in air conditioning. [24] A very recent study, however,
      using novel approaches examined whether ozone modified the associations between temperature
      and cardiovascular mortality in 95 large communities in the USA, 1987-2000, in summer. They
      found that a 10oC increase in temperature on the same day was associated with an increase in
      mortality by 1.17% and 8.31% for the lowest and highest level of ozone concentrations in all
      communities, respectively.[25]

      The purpose of this study is to perform the first controlled chamber study in order to
      understand the cardiovascular changes resulting from the interaction between heat and ozone.
      The information obtained from this study will enable the EPA to evaluate better the risks
      from air pollutants during a heat wave and provide advice on activities to mitigate the
      effects.
    

Intervention name(s): Clean Air; Ozone
Intervention type(s): Other; Other
Intervention description(s): Each subject will be exposed to clean air for 2 hours. The exposure atmosphere will be at a temperature between 31-34oC (88-93 oF) and approximately 40 + 10% RH. Subjects will exercise on a bike. Each exercise session will consist of a 15 minute exercise interval at a level of up to 25 L/min/m2BSA followed by a 15 minute rest period.; Each subject will be exposed up to 0.3ppm ozone for 2 hours. The exposure atmosphere will be at a temperature between 31-34oC (88-93 oF) and approximately 40 + 10% RH. Subjects will exercise on a bike. Each exercise session will consist of a 15 minute exercise interval at a level of up to 25 L/min/m2BSA followed by a 15 minute rest period.
Other intervention name(s): O3
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Controlled Human exposure study; Air Pollution; Temperature; Lung Function; Cardiovascular