Clinical trial NCT04109807: Effects of Low Dose Ozone on Airway Inflammatory Responses in Adults With Asthma - Sedentary Nasal Ozone (Asthma SNOZ)
Official title: Effects of Low Dose Ozone on Airway Inflammatory Responses in Adults With Asthma Asthma SNOZ
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: NA
Conditions: Asthma, Allergic
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Environmental Protection Agency (EPA)
name: North Carolina State University
First posted: 2019-09-30
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: To determine if low levels of ozone (O3) encountered on a typical day in Chapel Hill will decrease spirometric values in mild asthmatics.

Detailed description: 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 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.

Eligibility criteria: 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
* Proof of Covid Vaccination

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.
* Covid infection in the past 90 days

Primary outcomes:
measure: Change in Percent (%) predicted forced expiratory volume at one second (FEV1)
timeFrame: 6 hours post-O3 versus post-air exposure versus pre-exposure
Secondary outcomes:
measure: Change in Percent (%) predicted forced vital capacity (FVC)
timeFrame: 6 hours post-O3 versus post-air exposure versus pre-exposure
measure: Change in Percent eosinophils in induced sputum
timeFrame: 24 hours post-O3 versus post-air exposure
measure: Change in Percent (%) neutrophils in induced sputum
timeFrame: 24 hours post-O3 versus post-air exposure
measure: Change in Eosinophils per mg of induced sputum
timeFrame: 24 hours post-O3 versus post-air exposure
measure: Change in neutrophils per mg of induced sputum
timeFrame: 24 hours post-O3 versus post-air exposure
measure: Change in Cytokine concentrations in induced sputum picograms per milliliter (pg/mL)
timeFrame: 24 hours post-O3 versus post-air exposure
measure: Change in Cytokine concentrations in Nasal Epithelial Lining Fluid (NELF)
timeFrame: 6 hours post-O3 versus post-air exposure
measure: Change in Change in cytokine concentrations in Nasal Epithelial Lining Fluid (NELF)
timeFrame: 24 hours post-O3 versus post-air exposure
measure: Change in Fraction of Exhaled Nitric Oxide (FENO) levels in parts per billion (PPB)
timeFrame: 6 post-O3 post-air exposure versus pre-exposure
measure: Change in FENO levels in parts per billion (PPB)
timeFrame: 24 hours post-O3 versus post-air exposure
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina CEMALB
state: North Carolina
Study officials:
affiliation: UNC SOM
name: David Peden, MD
role: PRINCIPAL_INVESTIGATOR
References: