Effects of Low Dose Ozone on Airway Inflammatory Responses in Adults With Asthma - Sedentary Nasal Ozone (Asthma SNOZ)
Effects of Low Dose Ozone on Airway Inflammatory Responses in Adults With Asthma - Sedentary Nasal Ozone (Asthma SNOZ)
To determine if low levels of ozone (O3) encountered on a typical day in Chapel Hill will
 decrease spirometric values in mild asthmatics.
Short-term exposure to ambient air ozone has been recognized for decades to be adversely
 associated with impacts on the respiratory system. Indeed the evidence is such that the
 Environmental Protection Agency (EPA) has determined that there is a causal relationship, and
 even lowered the 8-hour exposure standard to 0.07 parts per million (ppm) in 2015. Controlled
 human exposure studies and epidemiological studies have consistently observed
 ozone-associated decrements in lung function and increased respiratory symptoms. Most
 controlled human exposure studies have been performed with high ozone concentrations.
 Additionally, epidemiologic studies have focused on populations engaged in outdoor activities
 (increasing ozone exposure through increased minute ventilation), or in cities such as Los
 Angeles or Mexico City where ambient ozone levels are especially high. Evidence has recently
 emerged that exposure to low ozone concentrations also produces adverse health effects,
 especially among susceptible groups including children with asthma.

 The University of North Carolina - North Carolina State University (UNC-NCSU) ASSIST group is
 examining the use of wearable technology that can measure levels of environmental pollutants
 and changes in physiologic parameters as potential adjuncts to the management of asthma. In
 ambient air, ozone (O3) is the most commonly encountered environmental trigger for asthma
 exacerbation, even at levels below the EPA standards of 0.120 ppm (1-hour average) and 0.07
 ppm (8-hour average). Environmental sensors that can monitor ozone exposure have been
 proposed to help high-risk patients avoid potential asthma triggers. The HET tracker has been
 proposed as one such system to provide personalized monitoring of ozone exposure. However,
 because devices that are based on user preferences are more likely to be adopted and used,
 data are needed on user experiences and preferences with wearable technology.

 It is also well established that poor symptom perception can reduce a patient's ability to
 recognize when their symptoms are worsening, thereby, decreasing the probability that they
 would take prophylactic action that could prevent further symptom progression and subsequent
 exacerbations. The negative impacts of asthma are largely preventable if patients engage in
 self-management behaviors, including symptom monitoring. The autonomic nervous system
 regulates physiologic responses like bronchoconstriction and mucus production, as well as
 heart rate (HR), heart rate variability (HRV) and respiratory rate (RR): all can be monitored
 continuously in daily life using wearable sensors. As an exploratory aim, the investigators
 wish to identify the capability of the HET devices to sense physiologic changes (suggestive
 of changes in autonomic tone, such as HRV) compared to gold standard monitors used in
 clinical practice.

 As part of the National Science Foundation (NSF) Nanosystems Engineering Research Center for
 Advanced Self-Powered Systems of Integrated Sensors and Technologies (ASSIST) Center,
 engineers at NCSU have been developing non-commercial technologies for achieving a
 high-performance and multi-functional biomedical sensing system while minimizing power
 consumption. The UNC-NC State ASSIST partnership developed the Health and Environmental
 Tracker (HET) testbed as a wireless ultra-low power system for correlated sensing of multiple
 environmental and health parameters.

 The objective of this study is to examine if low level ozone exposure (compared to a clean
 air exposure), reflective of a typical metropolitan summer day, will cause decrements in lung
 function and measurable upper and lower airway inflammation in mild asthmatics (who are not
 on asthma controller medications) while performing typical daily activities.
Inclusion Criteria:

 -  Ages 18-45, both sexes included

 -  Mild intermittent asthma, defined as daytime asthma symptoms no more than 2 times per
 week, night time asthma symptoms no more than 2 times per month, FEV1 >80% of
 predicted, and asthma exacerbation requiring oral steroids 1 time or less per year.

 -  Good general health as evidenced by medical history

 -  Vital signs will be within normal limits on admission to the study: oxygen saturation
 by pulse oximetry (SpO2) > 94%, systolic blood pressure between 150-90 mm Hg,
 diastolic blood pressure between 100-60 mm Hg, afebrile.

 -  FEV1 of at least 80% of predicted at baseline

 -  Able to provide informed consent

 Exclusion Criteria:

 -  Any chronic medical condition considered by the PI as a contraindication to the
 exposure study including significant cardiovascular disease, diabetes, chronic renal
 disease, chronic thyroid disease, history of chronic infections/immunodeficiency,
 history of tuberculosis

 -  Physician directed emergency treatment for an asthma exacerbation within the preceding
 12 months

 -  Orthopedic injuries or impediments that would preclude bicycle or treadmill exercise

 -  Viral upper respiratory tract infection within 4 weeks of challenge.

 -  Any acute infection requiring antibiotics within 4 weeks of exposure or fever of
 unknown origin within 2 weeks of challenge.

 -  Individuals who use daily controller medication for asthma. Pre-treatment with a short
 acting bronchodilator prior to exercise is allowed.

 -  Nasal surgery within 6 months

 -  Mental illness or history of drug or alcohol abuse that, in the opinion of the
 investigator, would interfere with the participant's ability to comply with study
 requirements.

 -  Any recent or current use of nicotine

 -  History of intubation for asthma

 -  Pregnancy or nursing an infant as EPA strictly prohibits intentional exposure for
 research to this population.