Acute Health Effects of Ozone Exposure

Acute Health Effects of Ozone Exposure in Healthy Young Adults: a Randomized Controlled Study

This is a randomized controlled human exposure crossover study. Investigators aim to investigate the acute health effects of ozone exposure in healthy young adults.

Study Overview

• Status: Completed
• Conditions: Pulmonary Function
• Intervention / Treatment: Other: 200 ppb ozone group; Other: 0 ppb ozone group

Detailed Description

The investigators will conduct a randomized controlled human exposure crossover study among 32 healthy young adults in Shanghai, China. Each subject will be exposed twice: once to clean air and once to 200 ppb ozone in a chamber for 2 hours. During the 2-hour exposure, each subject will be requested to alternate 20 minutes of rest and 10 minutes of exercise on a treadmill. The exercise workload will be adjusted to achieve the targeted ventilation of 25 ~ 27 L/min(approximately equal to 15 ~ 18L/min/m2 body surface area). Ozone will be generated by a silent electric discharge method (HTU-500, AZCO Industries Ltd., Canada) and introduced into the chamber. The temperature and relative humidity in the chamber will be maintained at 22±1℃ and 55%±5%, respectively. Health examinations will be conducted immediately prior to exposure, immediately after exposure, 2 hours after exposure and again the next morning. Health examinations include symptom questionnaire, skin tests, spirometry, and Holter monitoring. We plan to collect blood, buccal, urine, nasal secretion, saliva, exhaled breath condensate, sebum, and D-squame samples.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200032
    • Department of Environmental Health, School of Public Health, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Living in Shanghai during study period;
• Ability to complete the exercise to achieve the ventilation of 15 to 18 L/min/m2 body surface area;
• Body mass index >18.5 and ≤30.0 (30 is the lower limit for class 2 obesity for Chinese).

Exclusion Criteria:

• Smoking and alcohol abuse;
• Current drug and dietary supplements intake;
• Subjects with allergic diseases, such as allergic rhinitis, allergic asthma, and atopy;
• Subjects with cardiovascular diseases, such as congenital heart disease, pulmonary heart disease, and hypertension;
• Subjects with respiratory diseases, such as asthma, chronic bronchitis, and chronic obstructive pulmonary disease;
• Subjects with chronic diseases, such as diabetes, chronic hepatitis, and kidney disease;
• Subjects who have a history of major surgery;
• Abnormal spirometry (FEV1 and FVC ≤ 75% of predicted and FEV1/FVC ≤ 0.65);
• Abnormal baseline 12-lead resting electrocardiogram;
• Abnormal blood index, such as cell counting, blood lipids, and glutamic-pyruvic transaminase (GPT).

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: Exposure group; Subjects in exposure group will be exposed to 200 ppb ozone for 2 hours in a chamber.	Other: 200 ppb ozone group; The exposure group will be exposed to 200 ppb ozone in a chamber for 2 hours while alternating 20-min rest and 10-min exercise periods. The exercise workload will be adjusted to achieve the targeted ventilation of 25 ~ 27 L/min(approximately equal to 15 ~ 18L/min/m2 body surface area). The temperature and relative humidity in the chamber will be maintained at 22±1℃ and 55%±5%, respectively.
Sham Comparator: Control group; Subjects in control group will be exposed to 0 ppb ozone (clean air) for 2 hours in a chamber.	Other: 0 ppb ozone group; The control group will be exposed to 0 ppb ozone in a chamber for 2 hours while alternating 20-min rest and 10-min exercise periods. The exercise workload will be adjusted to achieve the targeted ventilation of 25 ~ 27 L/min(approximately equal to 15 ~ 18L/min/m2 body surface area). The temperature and relative humidity in the chamber will be maintained at 22±1℃ and 55%±5%, respectively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of FEV1	Changes of forced expiratory volume in 1 second	FEV1 will be examined immediately prior to exposure, immediately after exposure, 2 hours after exposure and again the next morning
Changes of FVC	Changes of forced vital capacity	FVC will be examined immediately prior to exposure, immediately after exposure, 2 hours after exposure and again the next morning

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HRV	Heart rate variability	Holter monitoring will be performed continuously for 24 hours.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in CRF concentrations between the two exposures	Difference in the serum concentrations of corticotrophin releasing factor between ozone exposure and filtered air exposure	2 hours after the completion of exposure.
Difference in ACTH concentrations between the two exposures	Difference in the serum concentrations of adrenocorticotropic hormone between ozone exposure and filtered air exposure	2 hours after the completion of exposure.
Difference in cortisol concentrations between the two exposures	Difference in the serum concentrations of cortisol between ozone exposure and filtered air exposure	2 hours after the completion of exposure
Difference in adrenaline concentrations between the two exposures	Difference in the serum concentrations of adrenaline between ozone exposure and filtered air exposure	2 hours after the completion of exposure.
Difference in noradrenaline concentrations between the two exposures	Difference in the serum concentrations of noradrenaline between ozone exposure and filtered air exposure	2 hours after the completion of exposure.
Change in the amount of skin moisture	Change in the amount of skin moisture, which was measure by a moisture meter. The number on the meter indicates how hydrated (or dehydrated) your skin is.	Immediately before exposure, 0.5 hours after the completion of exposure, and next morning.
Change in L-values	Change in skin color indicated by L-values, which was measured by a skin colorimeter.	Immediately before exposure, 0.5 hours after the completion of exposure, and next morning.
Change in a-values	Change in skin color indicated by a-values, which was measured by a skin colorimeter.	Immediately before exposure, 0.5 hours after the completion of exposure, and next morning.
Change in b-values	Change in skin color indicated by b-values, which was measured by a skin colorimeter.	Immediately before exposure, 0.5 hours after the completion of exposure, and next morning.
Difference in alpha diversity of microbiota between the two exposures	Difference in alpha diversity of microbiota in nasal secretions between ozone exposure and filtered air exposure	Immediately after the completion of exposure
Change in CC16 concentrations	Change in the serum concentrations of club cell protein	Immediately before exposure, 2 hours after the completion of exposure, and next morning
Differences in metabolite levels detected in serum metabolomics between the two exposures	Mass spectrometry-based serum metabolomics is non-targeted.The study is to find the differential metabolites in serum between ozone exposure and filtered air exposure.	2 hours after the completion of exposure
Differences in metabolite levels detected in airway metabolomics between the two exposures	Mass spectrometry-based metabolomics in exhaled breath condensate is non-targeted.The study is to find the differential metabolites in airway between ozone exposure and filtered air exposure.	2 hours after the completion of exposure
Differences in metabolite levels detected in urine metabolomics between the two exposures	Mass spectrometry-based urine metabolomics is non-targeted.The study is to find the differential metabolites in urine between ozone exposure and filtered air exposure.	Immediately after the completion of exposure
Differences in RNA expression levels detected in transcriptomics between the two exposures	Illumina-based transcriptomics is non-targeted. The study is to find the differentially expressed RNA between ozone exposure and filtered air exposure.	2 hours after the completion of exposure
Differences in protein levels detected in serum proteomics between the two exposures	Mass spectrometry-based proteomics in serum is non-targeted. The study is to find the differentially expressed proteins in serum between ozone exposure and filtered air exposure.	2 hours after the completion of exposure

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Haidong Kan, Ph.D, Department of Environmental Health, School of Public Health, Fudan University

Publications and helpful links

General Publications

• Niu Y, Chen R, Wang C, Wang W, Jiang J, Wu W, Cai J, Zhao Z, Xu X, Kan H. Ozone exposure leads to changes in airway permeability, microbiota and metabolome: a randomised, double-blind, crossover trial. Eur Respir J. 2020 Sep 3;56(3):2000165. doi: 10.1183/13993003.00165-2020. Print 2020 Sep. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2018
• Primary Completion (Actual): December 9, 2018
• Study Completion (Actual): October 12, 2019

Study Registration Dates

• First Submitted: September 30, 2018
• First Submitted That Met QC Criteria: October 3, 2018
• First Posted (Actual): October 5, 2018

Study Record Updates

• Last Update Posted (Actual): July 22, 2021
• Last Update Submitted That Met QC Criteria: July 16, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: FDUEH-5

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No