Asthma Exercise

Asthma incidence has risen steadily over the past 20 years and directly impacts the lives of millions (U.S.EPA, 2013). Currently, there are about 23 million people, including 7 million children affected by asthma (U.S.EPA, 2014). The Centers for Disease Control indicate an asthma prevalence rate of 8.4% in the United States (CDC, 2011). Additionally, asthma accounts for approximately 500,000 hospitalizations annually. It is also the third highest cause of hospitalization among children under 15. As asthma incidence continue to rise, the American Academy of Allergy, Asthma and Immunology (AAAAI) estimate the number of people with asthma to grow more than 100 million by 2025 (U.S.EPA, 2014).

Several different factors have been identified as

triggers for initiating a cycle for increasing asthma symptoms (U.S.EPA, 2013). Asthma is defined as an inflammatory disease of the respiratory airway generally persisting throughout a person’s lifetime. Inflammation causes obstruction to the airflow and causes an increased responsiveness to a variety of stimuli. Majority of asthma cases are associated with allergic responses to common airborne allergens such as household dust mites, pollens, animal dander, and molds disease (Diette et al., 2008). The disease has a specific genetic component and in predisposed individuals, exposure to allergens can lead to immunologic sensitization (Diette et al., 2008). Generally, pathophysiological determinants as well as asthma control and management programs may explain the continuous rise of the disease in the U.S. However, trends towards increased prevalence, mortality and economic cost of asthma have been observed in many other countries (U.S.EPA, 2014). Scientists point to the rapid increase in asthma incidence as irreconcilable by alterations in diagnostic categorization or gene pool (U.S.EPA, 2014). Therefore, there has been a growing attention towards the association between the environment and asthma.
General Public Health Problem- Ambient Ozone Overview
Through the Clean Air Act (CAA), the EPA established the National Ambient Air Quality Standards (NAAQS) for six common air pollutants, or criteria pollutants, including ground-level ozone, particulate matter, carbon monoxide, nitrogen oxides, sulfur dioxide and lead (U.S. EPA, 2006). These pollutants have been well examined determining adverse effects on health and the environment (U.S. EPA, 2006). Ground-level or ambient ozone is one of the two most ubiquitous and threatening air pollutants to human health in the United States, particulate matter being the second most hazardous (Samoli et al., 2011). It differs from protective ozone in the stratosphere, which aids in blocking harmful ultraviolet rays from reaching living organisms on Earth. Tropospheric ozone is a secondary air pollutant formed as a result of photochemical reactions between primary pollutants of nitrogen oxides (NOx) and volatile organic compounds (VOCs) (Pinto et al., 2009). Therefore, ozone is not directly emitted into the atmosphere, but rather is formed by chemical reactions between other air pollutants. Volatile organic compounds are released into the atmosphere from various sources such as: motor vehicles, refineries, chemical plants and also natural sources (Samoli et al., 2011). Even if ambient ozone forms at one location, it has potential to travel distances up to hundreds of miles (Hubbell et al., 2005). Despite its mobility, the formation of ambient ozone is preeminent in the presence of light winds allowing for ozone to remain concentrated near ground-level and vertical mixing in the atmosphere is suppressed (Hubbell et al., 2005). Moreover, photochemical activity involving precursors such as volatile organic compounds is enhanced during warmer seasons, due to the availability of sunlight and higher temperatures (U.S. EPA, 2014).
Ran et al. (2011) performed model simulations of volatile organic compound reactivity and its effects on ozone production suggesting that ozone production is sensitive to changes in its emissions. A study by Llusia and colleagues (2002) determined that volatile organic compound and ground-level ozone behave in a unique process driven by positive feedback. Ozone exposure increases the emissions of volatile organic compounds to the atmosphere, which in turn increases atmospheric ozone concentrations, due to volatile organic compounds’ part in the reactions leading to ozone formation (Llusia et al., 2002). It was further explored that increasing temperatures may play a major role in the positive feedback process.
Ozone Standards, Air Quality Index, and Ozone Monitoring
In 1971, the EPA first established primary and secondary National Ambient Air Quality Standards (NAAQS) for photochemical oxidants (U.S. EPA, 2014). Based on the Air Quality Criteria for Photochemical Oxidants Report (1970), standards were set to a level of 0.08 parts per million (ppm) for 1-hour average, not to be exceeded more than one hour per year. As mandated by the Clean Air Act (CAA), the EPA have to periodically review scientific bases for various NAAQS by examining new available information on a given criteria air pollutant (U.S. EPA, 2014). Years leading up to the recent past, proposals and reviews were presented to update the standard on more scientific based reasoning lead by health evidence. In 1997, the EPA proposed an update and replaced the 1-hour standard with 8-hour average ozone standard at a level of 0.08 ppm (U.S. EPA, 2014). In 2007, the EPA again proposed a revision of the then 8-hour average 0.08 ppm standard to a new standard within a range of 0.075 to 0.070 ppm (U.S. EPA, 2014). The Air Quality Criteria for Photochemical Oxidants Report (2006) was used to support the proposed decision, which presented latest information on air quality, exposure, health effects and environmental effects of ozone. A review with the final decision was made in 2008. The final rule stated a revised NAAQS for ozone reducing the level of 8-hour primary standard from 0.08 ppm to 0.75 ppm. Currently, this is the national standard by which state and local regions must adhere to. There is indication as of 2010 that EPA proposes to further lower the level within a range of 0.070 ppm to 0.060 ppm (U.S. EPA, 2014).
In order to monitor overall air quality the EPA developed the Air Quality Index (AQI). By converting air pollution concentrations originally in parts per million or micrograms per cubic meter, the figures are more comprehensible and comparable to each other. The conversion numbers completed fall within the range of zero to 500; above 100 is unhealthy, very unhealthy, or hazardous to health respective to the AQI number increasing (U.S. EPA, 2014). Air pollutants inspected in this index include carbon monoxide, nitrogen dioxide, ozone, sulfur dioxide, and particulate matter above and below 2.5 micrometers. By having the AQI, it is possible to approximate the general air quality in a geographic region. Additionally, the primary pollutant is obtainable in counties with pollutant monitoring sites; however, not all counties collect data daily or collect all or any of the pollutants (U.S. EPA, 2014). In 2010, there were over 1,300 state, local and tribal ozone monitors reporting concentrations to the EPA (U.S. EPA, 2014). The U.S. monitoring network has a greater urban focus. This is because the relationship between the precursor concentrations (NOx and VOCs) and ozone formation should be considered when determining monitoring stations (U.S. EPA, 1998). Urban and regional measurements are useful for determining trends, and designing area-wide control strategies (U.S. EPA, 1998). Monitoring stations may be placed downwind of the area having the highest precursor emissions to quantify ozone precursors such as VOCs (U.S. EPA, 1998).
Health Effects and Ozone Standard
Epidemiologic studies increasingly point to environmental factors as the primary cause of changes in disease prevalence (Holt, 1998).

The effect environmental factors have on the asthmatic populations can be better understood through the underlying cellular and molecular mechanisms (Holt, 1998). There has been extensive research over several decades in humans and animals yielding studies on mechanisms by which ozone exerts its effects. There are two main mechanisms by which asthma inflicted persons are more susceptible to adverse effects of ozone than to those without asthma. The first is that those with preexisting asthma might be more sensitive to ozone. Therefore, they experience respiratory symptoms and lung function changes common to all, but either at a lower concentration or with greater magnitude (U.S. EPA, 2014). Secondly, increased airway reactivity induced by ozone exposure may result in the worsening of a person’s underlying asthma status (U.S. EPA, 2014). Furthermore, repeated exposure to high levels of ozone concentration has been linked to new-onset asthma; individuals without preexisting asthma develop symptoms due to sensitization. Controlled exposure and some epidemiologic studies have demonstrated this response. Concern for excessive ambient ozone levels arises from ground-level ozone’s ability to cause acute respiratory response, significant lung capacity diminishment in at least 10-20% of healthy adults, pulmonary inflammation, impaired immune system,

asthma exacerbation, and damage to lung tissues (Strickland et al., 2010). Additionally, structural changes in the bronchiolar-alveolar transition region of the lung have been seen in experimental studies (U.S. EPA, 2006). As exposure to ozone destroys lung tissue, it is gradually replaced within a few days and repaired with new tissue, similar to the process of sunburned skin rejuvenation. If continuous exposure to ambient ozone occurs throughout a lifetime, it may result in a decreased quality of life.
It is well established that emergency department visits increase approximately twenty-four hours immediately following an increase in ozone levels past national ozone standards (Shao, 2008).

Ozone associated respiratory-related hospital admissions explain an estimated 2 to 3% of total respiratory-related admissions in urban case study locations (U.S. EPA, 2014). With every 4 degree Fahrenheit temperature increase in weather, ozone increases roughly by five percent (Shao, 2008). This is important to recognize throughout the summer months when asthma exacerbations are most frequent and ozone levels are higher. The severity of asthma varies significantly on a daily basis and increases as ozone levels also

increase.
In a study by Mortimer et al. (2002), 846 asthmatic children from eight U.S. urban areas were monitored during the summer time. Evidence found more than 10% decrement in peak expiratory flow (maximum speed of expiration), and an increased prevalence of respiratory symptoms for mornings following days of high ozone levels (Mortimer et al., 2002). In those with preexisting pulmonary disease, 10% or more decrement is large to be potentially highly severe (Samet, 2011). Generally, reduced respiratory function the morning after ozone days indicate worsening asthma status. Morning symptoms identified as coughing, chest tightness, and wheezing were associated with 0.030 ppm increase in the 8-hour average ozone level. A research performed in Athens, Greece over a four-year period (2001-2004) found significant association with asthma hospital admissions during the summer (Samoli et al., 2011). Moreover, the older age group of children 5-14 years old showed a significant association between ozone exposure and hospital admissions (Samoli et al., 2011). This is of particular interest because it implies adverse effects at higher ozone concentrations; children of that age group tend to spend more time outdoors than younger ones resulting higher exposure.
A retrospective cohort study by Lin et al. (2008) followed individuals born between the years 1995 and 1999 till their first asthma emergency admission in New York State. Birth and asthma hospitalizations were compared to data with ambient ozone concentrations (8-hour maximum) (Lin et al., 2008). The purpose of this study was to evaluate long-term or chronic exposure to ozone as it is less studied than short-term exposure. Chronic ozone exposure was defined using three indicators: mean concentration during the follow-up period, mean concentration during the ozone season, and proportion of follow-up days with ozone levels greater than 0.070 ppm (Lin et al., 2008). With a positive dose-response relationship, asthma admissions were significantly associated with increased ozone levels for all exposure indicators (Lin et al., 2008). They reported that chronic exposure to ground-level ozone may increase the risk of asthma hospitalizations (Lin et al., 2008).
Recent controlled human exposure studies on young, healthy adults with moderate exertion reported decreased forced expiratory volume (FEV) and lung inflammation after prolonged exposure to ozone concentrations as low as 0.060 ppm, and respiratory symptoms following exposures to concentrations as low as 0.070 ppm. Most studies have evidenced that an increase in ambient ozone exposures result in lung function decrements and increased emergency department visits, but there are several studies that report such relationship even for concentrations at the low end of the daily concentration scale. Schelegle et al. (2009) found that prolonged exposure to an average ozone concentration of 0.070 ppm resulted in a significant group mean 16% decrease in lung function. Prolonged exposure to 0.080 ppm concentrations with moderate exertion caused 29% decrease in lung function (Schelegle et al., 2009). Another study looking at healthy adults determined that concentrations at 0.075 ppm resulted in FEV decrements, respiratory symptoms and airway inflammation after 6.6-hour exposure (Kim et al., 2011).
Together, epidemiologic and experimental studies support a variety of respiratory insults associated with ozone exposure that can result in respiratory-related emergency department visits, hospital admissions, and/or mortality (U.S. EPA, 2014). There is strong indication and evidence that the current 0.075 ppm concentration standard may not be efficient in maintaining healthy standards. These studies bring awareness and support the consideration to revise the current standard, in order to provide increased public health protection against the range of health effects associated with ambient ozone. However, even with an update to stricter standards, there are still other methods such as better control strategies to consider. This is in part because of stressors like climate change, which may intensify the existing health effects and ozone concentrations.
Climate Change to Worsen Asthma Conditions and Ozone Air Quality
It has already been established that warmer temperatures increase the levels of ambient ozone, due the higher rate of photochemical reactivity of nitrogen oxides and volatile organic compounds in the presence of sunlight. Extensive research has been performed to reach the conclusion that the Earth’s climate is changing. The EPA states that average temperatures have risen across the 48 states since 1901 (U.S. EPA, 2012). In the past 30 years, scientists have measured an increased rate of warming, with seven of the top ten on record warmest years to have happened since 1990 (U.S. EPA, 2012). Moreover, the greatest increase in temperatures occurred in areas of the North, the West and Alaska (U.S. EPA, 2012). Such increases in temperature can lengthen ground-level ozone season, increase concentrations by 0.0020 to 0.008 ppm in certain regions, and further aggravate ozone concentrations on days the weather is already conducive to high ozone concentrations (U.S. EPA, 2009). Climate change is a challenge to reflect over since increasing temperatures will directly affect air quality, and therefore health impacts.  
B. Statement of the Problem
Evidence for asthma-related health effects have been extensively examined in relation to ambient ozone exposures. Mutually, a large amount of data ranging several decades supports the association between exposure to ozone and respiratory effects. While the majority of evidence has been shown through short-term exposures, recent epidemiologic studies demonstrate long-term exposure to also cause harm.
A study by Lehman et al. (2004) examined eastern U.S. with the area divided into five regions: Northeast, Great Lakes, Mid-Atlantic, Southwest, and Florida. Each of these regions presents unique spatial and temporal patterns of 8-hour ozone concentrations at non-urban sites from the years 1993 to 2002. The results found highest concentrations among all the regions generally to be in the Mid-Atlantic region. With such results, there is interest to additionally examine ozone concentrations within the Mid-Atlantic region.
In Pennsylvania every year, air pollution causes hundreds or thousands of missed days of work where individuals are afflicted with asthmatic symptoms such as shortness of breath and wheezing (Madeson & Wilcox, 2006). Using 2003 data by zip code, the annual public health damage from ground-level ozone in Pennsylvania resulted in: 7,000 respiratory hospital admissions, 300,000 asthma attacks, 1 million restricted activity days, and 4 million increased symptoms days (Madeson & Wilcox, 2006). As of 2006, the American Lung Association rates 28 counties in Pennsylvania with having poor air quality (Madeson & Wilcox, 2006). Because of the high prevalence of ozone related asthma effects, a study is warranted to further investigate an association for this region.
Health outcomes such as asthma have not been extensively studied in association with ambient ozone concentrations in the Pennsylvania State. Thus, a study of asthma-related hospitalization in all 67 Pennsylvania counties will be conducted to examine any potential associations between ambient ozone and asthma prevalence with existing secondary data sets. It is hypothesized that ambient ozone concentrations are associated with asthma hospitalization rates in Pennsylvania. Because volatile organic compound (VOC) is a known precursor to the development of ambient ozone, the study will also review if a relationship exists between VOC emissions and ozone in the same region. Therefore, it is also hypothesized that VOC emissions will be associated with ozone concentrations. The primary goal of this research is to increase awareness about asthma and the hazards of ambient ozone exposure as well as communicate the effects of climate change. As a secondary goal, the research is aimed to encourage public health officials to act on improving ozone conditions either by revision of the current standards or elicit comprehensive control on air pollution sources.  
C. Proposed Project Methods
Research Design
A cross-sectional ecological analysis will be conducted to examine 67 counties in Pennsylvania using secondary data sets for volatile organic compound emissions, ozone concentrations, and asthma hospitalization rates.
Methods
Volatile organic compound (VOC) gas emissions data will be obtained from Pennsylvania Department of Environmental Protection’s 2009 Ambient Air Quality Monitoring and Emission Trends Report. Through the Annual Emission Statement (AES) report submitted by industrial point sources, emission estimates are calculated as tons per year (TPY). Ambient ozone concentrations will be obtained from the U.S. Environmental Protection Agency through ozone monitoring sites located in each county. The data is presented as the fourth maximum daily 8-hour average in parts per million (ppm); this is the mean annual ozone concentration. Lastly, asthma hospitalization rates will be obtained from Pennsylvania Environmental Public Health Tracking’s Asthma Hospitalization Report as age-adjusted rate per 10,000 U.S. standard million population for each county. Data will be collected for each variable (VOC emission (TPY), ozone concentration (ppm), and asthma hospitalization rate) by county for the years 2004 through 2007.
There is a possibility of missing data due to lack of a monitoring station in a particular county, or because no emissions were reported for that pollutant. In such a case, those counties will be removed from the analysis process.

Statistical Analysis
All analyses will be conducted using The Statistical Package for Social Sciences (SPSS) 22.0. There are two sets of independent and dependent variable for each year (2004-2007) being investigated: (1) VOC emission (continuous) independent variable vs. ozone concentration (continuous) dependent variable, and (2) ozone concentration (continuous) independent variable vs. asthma hospitalization rate (continuous) dependent variable.
A Pearson’s Product-Moment Correlation (r) will be used to examine a linear relationship between: VOC emissions and ozone concentrations, and ozone concentration and asthma hospitalization rates. This is to assess the strength/magnitude and direction of the relationship between each independent variables and dependent variables.
A simple linear regression analysis will also be conducted to provide a statistical model explaining what leads to an increase or decrease in the dependent variable. It permits the relationship between variables to be described more accurately and if the independent variable is a good predictor of the dependent variable. Simple linear regression assumptions will be used to justify the use of linear regression for the purpose of prediction. Linearity tests the linear relationship between dependent and independent variables. Normality of residual error will check if there are any measurement errors in the predictor variables. Homoskedasticity will test for constant error variance across all values of the independent variable.
D. Expected Results
Pearson’s Product-Moment Correlation (r)
The expected results are that VOC emissions and ozone concentrations will have a statically significant positive relationship. Similarly, ozone concentration and asthma hospitalization rates will have a statistically significant positive relationship.
Simple Linear Regression
The assumptions should not be violated, so that linear regression analyses may proceed. VOC emissions should be a good predictor of ozone concentrations with a statically significant association. Likewise, ozone concentration will be a good predictor of asthma hospitalization rates with a statically significant association.

E. Statement of Public Health/Environmental Health significance
Ambient ozone is an criteria pollutant that induces a series of health effects ranging from increased respiratory symptoms, lung inflammation, damage to cells of respiratory tract, diminished lung function in healthy adults, and exacerbation of asthma. The illnesses often lead to an increase in hospitalization admissions for respiratory conditions. More than 100 million Americans live in areas where ozone concentrations exceed the Environmental Protection Agency’s 8-hour regulatory limit. Moreover, scientists have recommended that the current ozone limit or standard to be lowered due to insufficient protection of human health. The hyper-responsiveness of the respiratory system from consistent ambient ozone exposure is likely to worsen with increasing temperatures. Climate change is a present concern and with current emission trends, future generations are at risk for a greater threat. Public health action is warranted to curtail ambient ozone concentrations to reduce further respiratory health implications.