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 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.

Study Overview

• Status: Suspended
• Conditions: Asthma, Allergic
• Intervention / Treatment: Other: Ozone; Other: FA

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.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina CEMALB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 6 hour Filtered Air (FA) followed by O3 exposure; For the first exposure session, participants are exposed to filtered air (FA) for 6 hours. For the second exposure session, the same participant will be exposed to ozone at a concentration of 0.07ppm for 6 hours.	Other: Ozone; ozone exposure; Other: FA; Filtered air exposure
Experimental: 6 hour O3 exposure followed by FA exposure; For the first exposure session, a participant will be exposed to ozone at a concentration of 0.07ppm for 6 hours. For the second exposure session, the same participant will be exposed to FA for 6 hours.	Other: Ozone; ozone exposure; Other: FA; Filtered air exposure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Percent (%) predicted forced expiratory volume at one second (FEV1)	Change from baseline %predicted FEV1 post-O3 versus post-air exposure.	6 hours post-O3 versus post-air exposure versus pre-exposure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Percent (%) predicted forced vital capacity (FVC)	Change from baseline %predicted FVC post-O3 versus post-air exposure.	6 hours post-O3 versus post-air exposure versus pre-exposure
Change in Percent eosinophils in induced sputum	% eosinophils in induced sputum (24 hrs post ozone - post air)	24 hours post-O3 versus post-air exposure
Change in Percent (%) neutrophils in induced sputum	% neutrophils in induced sputum (24 hrs post ozone - post air)	24 hours post-O3 versus post-air exposure
Change in Eosinophils per mg of induced sputum	Eosinophils per mg of induced sputum (24 hrs post ozone - post air)	24 hours post-O3 versus post-air exposure
Change in neutrophils per mg of induced sputum	Neutrophils per mg of induced sputum (24 hrs post ozone - post air)	24 hours post-O3 versus post-air exposure
Change in Cytokine concentrations in induced sputum picograms per milliliter (pg/mL)	Cytokine and via Mesoscale in induced sputum (pg/mL)	24 hours post-O3 versus post-air exposure
Change in Cytokine concentrations in Nasal Epithelial Lining Fluid (NELF)	Cytokine via Mesoscale in NELF	6 hours post-O3 versus post-air exposure
Change in Change in cytokine concentrations in Nasal Epithelial Lining Fluid (NELF)	Cytokine and via Mesoscale in NELF	24 hours post-O3 versus post-air exposure
Change in Fraction of Exhaled Nitric Oxide (FENO) levels in parts per billion (PPB)	Changes in FeNO levels in ppb (6 hours post ozone - post air)	6 post-O3 post-air exposure versus pre-exposure
Change in FENO levels in parts per billion (PPB)	Changes in FeNO levels in ppb (24 hours post ozone - post air)	24 hours post-O3 versus post-air exposure

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: North Carolina State University; Environmental Protection Agency (EPA)
• Investigators: Principal Investigator: David Peden, MD, UNC SOM

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2019
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: September 23, 2019
• First Submitted That Met QC Criteria: September 27, 2019
• First Posted (Actual): September 30, 2019

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 18-2425

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
• IPD Sharing Time Frame: 9 to 36 months following publication
• IPD Sharing Access Criteria: Approval from an IRB, IEC, or REB and an executed data use/sharing agreement with UNC.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No