Original article
Effect of ozone on allergic airway inflammation

https://doi.org/10.1016/j.jacig.2022.05.007Get rights and content
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open access

Background

Exposure to ozone (O3) is associated with increased risk of exacerbations of asthma, but the underlying mechanisms are not well studied.

Objective

We sought to determine whether O3 exposure would enhance airway inflammatory responses to allergen and the GSTM1-null genotype would modulate this enhancement.

Methods

In a crossover design, 10 asthmatic participants (5 with GSTM1-null genotype) who had specific sensitization to Dermatophagoides pteronyssinus (DP) were exposed to 160 ppb O3 or filtered air (FA) control for 4 hours on 2 separate days at least 3 weeks apart. At 20 hours after exposure, endobronchial challenge with DP allergen, and sham normal saline (NS) instillation, were performed in separate bronchi. Six hours later, a second bronchoscopy was performed to collect bronchoalveolar lavage (BAL) from the DP- and NS-challenged segments for analyses of inflammatory biomarkers. Linear regression compared cell and cytokine responses across the 4 exposure groups (FA-NS, O3-NS, FA-DP, O3-DP). Effect modification by GSTM1 genotype was assessed in stratified regressions.

Results

BAL eosinophil counts were increased in segments challenged with DP compared to sham-challenged segments (P < .01). DP challenge compared to sham also caused a significant increase in BAL concentrations of the TH2 cytokines IL-4, IL-5, IL-10, and IL-13 (P < .03 for all comparisons). O3 exposure did not significantly affect BAL cells or cytokine after DP challenge. Compared to GSTM1-present participants, GSTM1-null participants had significantly lower eosinophil (P < .041) and IL-4 (P < .014) responses to DP challenge after O3 exposure.

Conclusions

While O3 did not cause a clear differential effect on airway inflammatory responses to allergen challenge, those responses did appear to be modulated by the antioxidant enzyme, GSTM1.

Key words

Ozone
allergen
airway inflammation
glutathione S-transferase mu

Abbreviations used

ATS
American Thoracic Society
BAL
Bronchoalveolar lavage
DP
Dermatophagoides pteronyssinus
FA
Filtered air
FVC
Forced vital capacity
GM-CSF
Granulocyte macrophage colony-stimulating factor
GST
Glutathione S-transferase
LEAC
Local endobronchial allergen challenge
NS
Normal saline
RML
Right middle lobe
ROS
Reactive oxygen species
RUL
Right upper lobe

Cited by (0)

Supported by California Air Resources Board (CARB) contract 03-315 (to J.R.B.), National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute K23 HL083099 (to M.A.), and NIH/National Center for Research Resources, University of California, San Francisco–Clinical and Translational Science Institute grant UL1 RR024131. The contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of either CARB or the NIH.

Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.